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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 685 records · Page 38
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Measuring the spin polarization of alkali-metal atoms using nuclear magnetic resonance frequency shifts of noble gases

We report a novel method of measuring the spin polarization of alkali-metal atoms by detecting the NMR frequency shifts of noble gases. We calculated the profile of {sup 87}Rb D1 line absorption cross sections. We then measured the absorption profile of the sample cell, from which we calculated the {sup 87}Rb number densities at different temperatures. Then we measured the frequency shifts resulted from the spin polarization of the {sup 87}Rb atoms and calculated its polarization degrees at different temperatures. The behavior of frequency shifts versus temperature in experiment was consistent with theoretical calculation, which may be used as compensative signal for the NMRG closed-loop control system.

36 MATERIALS SCIENCE↗
DOE OSTI2015

High-temperature nuclear magnetic resonance study of phase transition kinetics in LiNaSO{sub 4}

A new high-temperature NMR technique for measurements of the phase transition kinetics in solids has been developed. The technique allows measuring the time evolution of the volume of the appearing phase at controlled cooling rates. Developed method was applied to study the phase transition kinetics in the superionic conductor LiNaSO{sub 4}. It was revealed that the phase transition in LiNaSO{sub 4} is governed by the diffusion-controlled growth of nuclei (“germs”). An effect of the crystallite rearrangement in the LiNaSO{sub 4} powder after cooling through the phase transition was also revealed. This effect was studied by means of high-temperature XRD and NMR.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2014

Difference between healthy children and ADHD based on wavelet spectral analysis of nuclear magnetic resonance images

The main goal of this project was to create a computer algorithm based on wavelet analysis of region of homogeneity images obtained during resting state studies. Ideally it would automatically diagnose ADHD. Because the cerebellum is an area known to be affected by ADHD, this study specifically analysed this region. Male right handed volunteers (infants with ages between 7 and 11 years old) were studied and compared with age matched controls. Statistical differences between the values of the absolute integrated wavelet spectrum were found and showed significant differences (p<0.0015) between groups. This difference might help in the future to distinguish healthy from ADHD patients and therefore diagnose ADHD. Even if results were statistically significant, the small size of the sample limits the applicability of this methods as it is presented here, and further work with larger samples and using freely available datasets must be done.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Observing the Surface Termination of LaScO 3 Perovskite Using Solid-State Nuclear Magnetic Resonance

Materials with well-defined surfaces are drawing increased attention for the design of bespoke catalysts and nanomaterials. Gaining a detailed understanding of the surfaces of these materials is an important challenge, which is often complicated by surface polymorphism and dynamic restructuring. We introduce the use of surface-enhanced NMR spectroscopy for the observation of such surfaces, focusing on LaScO 3 as an example. Here, we show that double-resonance NMR experiments correlating surface oxygen and probe molecules to the 139 La and 45 Sc nuclei at the surface reveal the material to be terminated by a ScO x monolayer. Surface-selective 17 O and 45 Sc NMR experiments further showed the material to be hydroxyl terminated and that the surface may be prone to dynamic restructuring as a result of moisture exposure. Perhaps most interestingly, surface-selective 139 La NMR experiments revealed the existence of previously undetected surface lanthanum defects, suggesting that surface-enhanced NMR may be useful as a guide in the synthesis of defect-free surfaces in the design of various nanomaterials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2015

Fragment-based {sup 13}C nuclear magnetic resonance chemical shift predictions in molecular crystals: An alternative to planewave methods

We assess the quality of fragment-based ab initio isotropic {sup 13}C chemical shift predictions for a collection of 25 molecular crystals with eight different density functionals. We explore the relative performance of cluster, two-body fragment, combined cluster/fragment, and the planewave gauge-including projector augmented wave (GIPAW) models relative to experiment. When electrostatic embedding is employed to capture many-body polarization effects, the simple and computationally inexpensive two-body fragment model predicts both isotropic {sup 13}C chemical shifts and the chemical shielding tensors as well as both cluster models and the GIPAW approach. Unlike the GIPAW approach, hybrid density functionals can be used readily in a fragment model, and all four hybrid functionals tested here (PBE0, B3LYP, B3PW91, and B97-2) predict chemical shifts in noticeably better agreement with experiment than the four generalized gradient approximation (GGA) functionals considered (PBE, OPBE, BLYP, and BP86). A set of recommended linear regression parameters for mapping between calculated chemical shieldings and observed chemical shifts are provided based on these benchmark calculations. Statistical cross-validation procedures are used to demonstrate the robustness of these fits.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2011

Electron density distribution in BaPb{sub 1-x}Sb{sub x}O{sub 3} superconducting oxides studied by double nuclear magnetic resonance methods

The effect of charge disorder on the formation of an inhomogeneous state of the electron system in the conduction band in BaPb{sub 1-x}Sb{sub x}O{sub 3} superconducting oxides is investigated experimentally by NMR methods. The NMR spectra of {sup 17}O are measured systematically, and the contributions from {sup 17}O atoms with different cation nearest surroundings are identified. It is found that microscopic regions with an elevated spin density of charge carriers are formed within two coordination spheres near antimony ions. Nuclei of the superconducting phase of the oxide (regions with an elevated antimony concentration) microscopically distributed over the sample are detected in compounds with x = 0.25 and 0.33. Experiments in which a double resonance signal of the spin echo of {sup 17}O-{sup 207}Pb and {sup 17}O-{sup 121}Sb are measured in the metal phase of BaPb{sub 1-x}Sb{sub x}O{sub 3} oxides are carried out for the first time. The constants of indirect heteronuclear spin-spin {sup 17}O-{sup 207}Pb interaction are determined as functions of the local Knight shift {sub 207}Ks. The estimates of the constants of the indirect interaction between the nuclei of the nearest neighbors (O-Pb and Pb-Pb atoms) and analysis of evolution of the NMR spectra of {sup 17}O upon a change in the antimony concentration are convincing evidence in favor of the development of a microscopically inhomogeneous state of the electron system in the metal phase of BaPb{sub 1-x}Sb{sub x}O{sub 3} oxides.

36 MATERIALS SCIENCE↗
DOE OSTI2011

Site-specific solvent exposure analysis of a membrane protein using unnatural amino acids and {sup 19}F nuclear magnetic resonance

Highlights: {yields} Solvent isotope shift analysis of {sup 19}F-tfmF in different H{sub 2}O/D{sub 2}O molar ratio. {yields} Correlation between solvent isotope shift of {sup 19}F-spins and solvent exposure analysis. {yields} Solvent exposure analysis of membrane proteins. -- Abstract: Membrane proteins play an essential role in cellular metabolism, transportation and signal transduction across cell membranes. The scarcity of membrane protein structures has thus far prevented a full understanding of their molecular mechanisms. Preliminary topology studies and residue solvent exposure analysis have the potential to provide valuable information on membrane proteins of unknown structure. Here, a {sup 19}F-containing unnatural amino acid (trimethylfluoro-phenylalanine, tfmF) was applied to accomplish site-specific {sup 19}F spin incorporation at different sites in diacylglycerol kinase (DAGK, an Escherichia coli membrane protein) for site-specific solvent exposure analysis. Due to isotope effect on {sup 19}F spins, a standard curve for {sup 19}F-tfmF chemical shifts was drawn for varying solvent H{sub 2}O/D{sub 2}O ratios. Further site-specific {sup 19}F solvent isotope shift analysis was conducted for DAGK to distinguish residues in water-soluble loops, interfacial areas or hydrophobic membrane regions. This site-specific solvent exposure analysis method could be applied for further topological analysis of other membrane proteins.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

High-pressure magic angle spinning nuclear magnetic resonance

A high-pressure magic angle spinning (MAS) NMR capability, consisting of a reusable high-pressure MAS rotor, a high-pressure rotor loading/reaction chamber for in situ sealing and re-opening of the high-pressure MAS rotor, and a MAS probe with a localized RF coil for background signal suppression, is reported. The unusual technical challenges associated with development of a reusable high-pressure MAS rotor are addressed in part by modifying standard ceramics for the rotor sleeve by abrading the internal surface at both ends of the cylinder. In this way, not only is the advantage of ceramic cylinders for withstanding very high-pressure utilized, but also plastic bushings can be glued tightly in place so that other removable plastic sealing mechanisms/components and O-rings can be mounted to create the desired high-pressure seal. Using this strategy, sealed internal pressures exceeding 150 bars have been achieved and sustained under ambient external pressure with minimal loss of pressure for 72 h. Finally, as an application example, in situ 13 C MAS NMR studies of mineral carbonation reaction intermediates and final products of forsterite (Mg 2 SiO 4 ) reacted with supercritical CO 2 and H 2 O at 150 bar and 50 °C are reported, with relevance to geological sequestration of carbon dioxide.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2019

Magnetic resonance imaging findings of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion in adults: a pilot study

Purpose: The purpose of the study was to retrospectively analyze MRI findings of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2/TFE RCC) in adults. Methods: Sixteen patients with Xp11.2/TFE RCC were reviewed retrospectively. The clinical characteristics and imaging features were assessed and then compared between metastatic and non-metastatic subgroups. Results: The mean age at diagnosis was 47.4 (20–76) years. Seven (44 %) patients were men, and nine (56 %) patients were women. The lesions predominantly exhibited an endophytic distribution (n = 14, 88 %) with a capsule (n = 16, 100 %), accompanied by solid and cystic patterns (n = 12, 75%) and hemorrhage (n = 11, 69 %). The tumors prevalently appeared hyper- to isointense on T1WI (n = 14, 88 %), hypointense on T2WI (n = 13, 81 %), and hyperintense on DWI (n = 16, 100 %) with a lower ADC (P < 0.001) than that of the surrounding tissue. The tumors were less enhanced than the normal renal cortex in all phases with a prolonged enhancement pattern (P ≤ 0.001). In addition, six patients (38 %) developed recurrence or metastases. The RCCs with metastases showed an irregular shape (P = 0.013), an incomplete capsule (P = 0.018), heterogeneous solid-cystic patterns (P = 0.034), and hemorrhage (P = 0.037) than non-metastatic subgroups. Conclusions: MRI provides valuable information for the diagnosis of adult Xp11.2/TFE RCCs. Features including irregular shape, incomplete capsule, mixed solid-cystic pattern, and hemorrhage may indicate the occurrence of recurrence or metastases.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Magnetic resonance elastography SE-EPI vs GRE sequences at 3T in a pediatric population with liver disease

Purpose: The goal of our study is to compare hepatic stiffness measures using gradient-recalled echo (GRE) versus spin-echo echo planar imaging (SE-EPI)-based MR Elastography (MRE) at 3T used to measure hepatic stiffness in a patients with suspected liver diseases. Materials and methods: This retrospective study included 52 patients with liver disease who underwent a 3T MRE exam including both an investigational SE-EPI-based technique and a product GRE-based technique. Regions of interest (ROI) were placed on the elastograms to measure elastography-derived liver stiffness as well as the area included within the ROIs. The mean liver stiffness values and area of ROIs were compared. Results: The mean liver stiffness was 3.72 kilopascal (kPa) ± 1.29 using GRE MRE and 3.78 kPa ± 1.13 using SE-EPI MRE. Measurement of liver stiffness showed excellent agreement between the two pulse sequences with a mean bias of − 0.1 kPa (range − 1.8 to 1.7 kPa) between sequences. The mean measurable ROI area was higher with SE-EPI (313.8 cm{sup 2} ± 213.8) than with the GRE technique (208.6 cm{sup 2} ± 114.8), and the difference was statistically significant (P < 0.05). Conclusions: Our data shows excellent agreement of measured liver stiffness between GRE and SE-EPI-based sequences at 3T. Our results show the advantage of a SE-EPI MRE sequence in terms of image quality, ROI size and acquisition time with equivalent liver stiffness measurements as compared to GRE-MRE sequence.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Efficiency Improvement in a Busy Radiology Practice: Determination of Musculoskeletal Magnetic Resonance Imaging Protocol Using Deep-Learning Convolutional Neural Networks

The purposes of this study are to evaluate the feasibility of protocol determination with a convolutional neural networks (CNN) classifier based on short-text classification and to evaluate the agreements by comparing protocols determined by CNN with those determined by musculoskeletal radiologists. Following institutional review board approval, the database of a hospital information system (HIS) was queried for lists of MRI examinations, referring department, patient age, and patient gender. These were exported to a local workstation for analyses: 5258 and 1018 consecutive musculoskeletal MRI examinations were used for the training and test datasets, respectively. The subjects for pre-processing were routine or tumor protocols and the contents were word combinations of the referring department, region, contrast media (or not), gender, and age. The CNN Embedded vector classifier was used with Word2Vec Google news vectors. The test set was tested with each classification model and results were output as routine or tumor protocols. The CNN determinations were evaluated using the receiver operating characteristic (ROC) curves. The accuracies were evaluated by a radiologist-confirmed protocol as the reference protocols. The optimal cut-off values for protocol determination between routine protocols and tumor protocols was 0.5067 with a sensitivity of 92.10%, a specificity of 95.76%, and an area under curve (AUC) of 0.977. The overall accuracy was 94.2% for the ConvNet model. All MRI protocols were correct in the pelvic bone, upper arm, wrist, and lower leg MRIs. Deep-learning-based convolutional neural networks were clinically utilized to determine musculoskeletal MRI protocols. CNN-based text learning and applications could be extended to other radiologic tasks besides image interpretations, improving the work performance of the radiologist.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Computed tomographic perfusion with 160-mm coverage: comparative analysis of hepatocellular carcinoma treated by two transarterial chemoembolization courses relative to magnetic resonance imaging findings

Purpose: The aim of this study was to assess hepatocellular carcinoma (HCC) response with CT perfusion parameters before and after two transarterial chemo embolization (TACE) courses compared with MRI, and to search for predictive factors of response. Methods: 37 lesions (19 patients) were included between October 2015 and September 2017, based on the Barcelona Clinic Liver Cancer guidelines. CT perfusion with 160-mm coverage and MRI were performed before and after the first TACE course, and after the second TACE course. Quantitative perfusion parameters were compared to the response assessed with MRI using mRECIST criteria, defining response groups: complete response (CR), partial response (PR), no response (NR), response (including CR and PR), no complete response (NCR, including PR and NR). Results: Pre-TACE blood flow (BF) and hepatic arterial blood flow (HABF) were significantly higher in lesions with post-TACE 1 CR than in those with NCR (BF: 118.8 vs. 76.3 mL/100 g/min, p = 0.0231; HABF: 76 vs. 44.2 mL/100 g/min, p = 0.0112). Pre-TACE time to peak (TTP) and mean transit time (MTT) were significantly lower in lesions with post-TACE 2 response than in those with NR (TTP: 31.5 vs. 46.1 s, p = 0.0313; MTT: 15.8 vs. 22.8 s, p = 0.0204). Post-TACE 1 and post-TACE 2 perfusion parameters did not exhibit any statistically significant differences relative to MRI response. Conclusion: Our study did not find, after a first TACE course, perfusion parameters associated with a response to a second TACE course. However, baseline perfusion parameters analysis could lead to better therapeutic management of HCC by targeting lesions likely to respond well to TACE courses.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Combined Static and Dynamic Computed Tomography Angiography of Peripheral Artery Occlusive Disease: Comparison with Magnetic Resonance Angiography

PurposeTo compare in patients with known peripheral artery occlusive disease (PAOD), image quality of a combined CTA to a combined MRA protocol, including both static and dynamic acquisitions.Materials and MethodsTwenty-two patients with PAOD were examined with a combined CTA and MRA protocol consisting of static acquisitions (s-CTA, s-MRA) of the entire runoff and dynamic acquisitions (d-CTA, d-MRA) of the calves. Two radiologists compared image quality of the s-MRA versus s-CTA as well as d-MRA versus d-CTA. Image quality was assessed on a segmental basis using a 4-point Likert scale.ResultsFor s-CTA, 76% of segments were rated as excellent or good. For s-MRA, 50% of segments were rated as excellent or good (p < 0.0001). For d-CTA, median image quality score for all segments was rated as excellent for both readers. For d-MRA, median image quality for the different segments ranged from moderate to good. For both d-CTA and d-MRA, the median image quality scores were significantly higher for all segments of the lower limb compared with the static examinations of the lower limb segments (all p values < 0.0001). In patients with PAOD category 4–6, 80% of segments were rated as excellent or good for d-CTA, while 45% of segments were rated as poor or non-diagnostic for d-MRA.ConclusionIn patients with known PAOD, a combined static and dynamic CTA examination improves image quality relative to static and dynamic MRA and should be considered as an alternative to MRA, particularly in patients with advanced stage PAOD.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

A Large Sample Volume Magic Angle Spinning Nuclear Magnetic Resonance Probe for In-Situ Investigations with Constant Flow of Reactants

A large-sample-volume constant-flow magic angle sample spinning (CF-MAS) NMR probe is reported for in-situ studies of the reaction dynamics, stable intermediates/transition states, and mechanisms of catalytic reactions. In our approach, the reactants are introduced into the catalyst bed using a fixed tube at one end of the MAS rotor while a second fixed tube, linked to a vacuum pump, is attached at the other end of the rotor. The pressure difference between both ends of the catalyst bed inside the sample cell space forces the reactants flowing through the catalyst bed, which improves the diffusion of the reactants and products. This design allows the use of a large sample volume for enhanced sensitivity and thus permitting in-situ 13C CF-MAS studies at natural abundance. As an example of application, we show that reactants, products and reaction transition states associated with the 2-butanol dehydration reaction over a mesoporous silicalite supported heteropoly acid catalyst (HPA/meso-silicalite-1) can all be detected in a single 13C CF-MAS NMR spectrum at natural abundance. Coke products can also be detected at natural 13C abundance and under the stopped flow condition. Furthermore, 1H CF-MAS NMR is used to identify the surface functional groups of HPA/meso-silicalite-1 under the condition of in-situ drying . We also show that the reaction dynamics of 2-butanol dehydration using HPA/meso-silicalite-1 as a catalyst can be explored using 1H CF-MAS NMR.

01 COAL, LIGNITE, AND PEAT↗
DOE OSTI2022

Atomic-Level Structure of Mesoporous Hexagonal Boron Nitride Determined by High-Resolution Solid-State Multinuclear Magnetic Resonance Spectroscopy and Density Functional Theory Calculations

Mesoporous hexagonal boron nitride (p-BN) has received significant attention over the last decade as a promising candidate for water cleaning/pollutant removal and hydrogen storage applications. In this work, high-resolution solid-state NMR spectroscopy and plane-wave density-functional theory (DFT) calculations are used to obtain an atomic-level description of p-BN. 1 H– 15 N or 1 H– 14 N heteronuclear (HETCOR) correlation experiments recorded with either conventional NMR at room temperature or dynamic nuclear polarization surface-enhanced spectroscopy (DNP-SENS) at ca. 100 K reveal NB 2 H, NBH 2 , NBH 3 + species residing on the edges of BN sheets. Ultra-high field 35.2 T 11 B NMR spectroscopy was used to resolve 11 B NMR signals from BN 3 , BN 2 O x (OH) 1–x (x = 0–1), BNO x (OH) 2–x (x = 0–2), BO x (OH) 3–x (x = 0–3), and BO x (OH) 4–x – (x = 0–4). Importantly, 2D 11 B dipolar double-quantum–single-quantum homonuclear correlation spectra reveal that many pore/defect sites are composed of boron oxide/hydroxide clusters connected to the BN framework through BN 2 O units. 1D and 2D 11 B{ 15 N} HETCOR NMR experiments, in addition to plane-wave DFT calculations of nine different structural models, further confirm the assignment of all NMR signals. The detailed structure determination of the pore and edge/defect sites within p-BN should further enable the rational design and development of next-generation p-BN-based materials. In addition, the techniques outlined here should be applicable to determine structure within other porous and/or boron-based materials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2012

Proton nuclear magnetic resonance studies of hydrogen diffusion and electron tunneling in Ni-Nb-Zr-H glassy alloys

Using the Fourier transform of the echo envelope, the proton line shapes, spin-lattice relaxation time, and spin-spin relaxation time have been measured in a (Ni{sub 0.36}Nb{sub 0.24}Zr{sub 0.40}){sub 90}H{sub 10} glassy alloy at 1.83 T ({approx}78 MHz) and at temperatures between 1.8 and 300 K. First, the spectral line width decreases abruptly between 1.8 and 2.1 K. Next, it remains almost constant at 13 kHz up to {approx}150 K. Finally, the line width decreases as the temperature increases from {approx}150 to 300 K. The initial decrease in the spectral line width is ascribed to the distribution of the external field, which is caused by the penetration of vortices in the superconducting state. The subsequent leveling off in the spectral line width is ascribed to the dipole-dipole interaction between protons when hydrogen atoms are trapped into vacancies among the Zr-centered icosahedral Zr{sub 5}Ni{sub 5}Nb{sub 3} clusters. The final decrease in the spectral line width is ascribed to the motional narrowing of the width that is caused by the movement of hydrogen atoms. The temperature dependences of the spin-lattice and spin-spin relaxation time showed that at temperature above 150 K and the activation energy of 8.7 kJ/mol allowed the hydrogen atoms to migrate among the clusters. The distance between the hydrogen atoms is estimated to be 2.75 A. Hydrogen occupancies among clusters in the (Ni{sub 0.36}Nb{sub 0.24}Zr{sub 0.40}){sub 90}H{sub 10} glassy alloy play an important role in the diffusion behavior and in the electronic properties of this alloy.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2021

Proton Nuclear Magnetic Resonance (H NMR) of Glycolate in Real Waste: Developing and Testing Analytical Methods for the Savannah River Site Liquid Waste System

In preparation for implementing the NG acid flowsheet for the SRS LWS, analytical methods for determining glycolate at low concentration are desired to support system management and safety. Previous work documented that the IC method performed well for samples with low to moderate ionic strength. That work also included a scoping effort to determine if an alternate analytical strategy using H NMR would complement and extend the capabilities of the IC method. The H NMR scoping results indicated that the method had the potential to expand glycolate analysis in LWS samples to higher ionic strength tanks/solutions. The scope of this work is to develop innovative proton NMR techniques, including demonstrating ion exchange decontamination protocols needed for application of the technique to real waste samples. Part of radioactive waste processing at SRS uses formic acid to reduce oxidized (Hg 2+ ) to more volatile elemental Hg for steam striping, collecting, and disposal. Under acidic conditions found in the Chemical Processing Cell (CPC) at the Defense Waste Processing Facility (DWPF), formic acid has a much higher hydrogen generation rate than an alternative reductant, glycolic acid. Thus, an NG acid flowsheet has been developed utilizing glycolic acid with the benefit of easing the need for headspace monitoring requirements for hydrogen and ammonia at DWPF. Low concentrations of glycolate are conservatively assumed to be in the recycle stream, which will collect in the Recycle Collection Tank (RCT). The DWPF recycle stream collected in the RCT has a distinct pathway to the LWS waste tanks that feed the 2H and 3H Evaporator. This route involves transfer of the DWPF recycle to Tank 22 in the Concentration, Storage, and Transfer Facilities (CSTF) followed by transfer to the LWS tank farm/evaporators.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2011

Crystallographic and Nuclear Magnetic Resonance Evaluation of the Impact of Peptide Binding to the Second PDZ Domain of Protein Tyrosine Phosphatase 1E

PDZ (PSD95/Discs large/ZO-1) domains are ubiquitous protein interaction motifs found in scaffolding proteins involved in signal transduction. Despite the fact that many PDZ domains show a limited tendency to undergo structural change, the PDZ family has been associated with long-range communication and allostery. One of the PDZ domains studied most in terms of structure and biophysical properties is the second PDZ ('PDZ2') domain from protein tyrosine phosphatase 1E (PTP1E, also known as PTPL1). Previously, we showed through NMR relaxation studies that binding of the RA-GEF2 C-terminal peptide substrate results in long-range propagation of side-chain dynamic changes in human PDZ2 [Fuentes, E. J., et al. (2004) J. Mol. Biol. 335, 1105-1115]. Here, we present the first X-ray crystal structures of PDZ2 in the absence and presence of RA-GEF2 ligand, determined to resolutions of 1.65 and 1.3 {angstrom}, respectively. These structures deviate somewhat from previously determined NMR structures and indicate that very minor structural changes in PDZ2 accompany peptide binding. NMR residual dipolar couplings confirm the crystal structures to be accurate models of the time-averaged atomic coordinates of PDZ2. The impact on side-chain dynamics was further tested with a C-terminal peptide from APC, which showed results nearly identical to those of RA-GEF2. Thus, allosteric transmission in PDZ2 induced by peptide binding is conveyed purely and robustly by dynamics. {sup 15}N relaxation dispersion measurements did not detect appreciable populations of a kinetic structural intermediate. Collectively, for ligand binding to PDZ2, these data support a lock-and-key binding model from a structural perspective and an allosteric model from a dynamical perspective, which together suggest a complex energy landscape for functional transitions within the ensemble.

59 BASIC BIOLOGICAL SCIENCES↗