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Cao, Y

Publications and source records attributed to Cao, Y.

At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

TH-A-9A-04: Incorporating Liver Functionality in Radiation Therapy Treatment Planning

Purpose: Liver SBRT patients have both variable pretreatment liver function (e.g., due to degree of cirrhosis and/or prior treatments) and sensitivity to radiation, leading to high variability in potential liver toxicity with similar doses. This work aims to explicitly incorporate liver perfusion into treatment planning to redistribute dose to preserve well-functioning areas without compromising target coverage. Methods: Voxel-based liver perfusion, a measure of functionality, was computed from dynamic contrast-enhanced MRI. Two optimization models with different cost functions subject to the same dose constraints (e.g., minimum target EUD and maximum critical structure EUDs) were compared. The cost functions minimized were EUD (standard model) and functionality-weighted EUD (functional model) to the liver. The resulting treatment plans delivering the same target EUD were compared with respect to their DVHs, their dose wash difference, the average dose delivered to voxels of a particular perfusion level, and change in number of high-/low-functioning voxels receiving a particular dose. Two-dimensional synthetic and three-dimensional clinical examples were studied. Results: The DVHs of all structures of plans from each model were comparable. In contrast, in plans obtained with the functional model, the average dose delivered to high-/low-functioning voxels was lower/higher than in plans obtained with its standard counterpart. The number of high-/low-functioning voxels receiving high/low dose was lower in the plans that considered perfusion in the cost function than in the plans that did not. Redistribution of dose can be observed in the dose wash differences. Conclusion: Liver perfusion can be used during treatment planning potentially to minimize the risk of toxicity during liver SBRT, resulting in better global liver function. The functional model redistributes dose in the standard model from higher to lower functioning voxels, while achieving the same target EUD and satisfying dose limits to critical structures. This project is funded by MCubed and grant R01-CA132834.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal vascular response to radiation could be sex and age dependent. The early hippocampal vascular dose-response could predict late neurocognitive dysfunction. (Support: NIH-RO1NS064973)

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-C-17A-01: MRI-Based Radiotherapy Treatment Planning In Pelvis

Purpose: To support radiotherapy dose calculation, synthetic CT (MRCT) image volumes need to represent the electron density of tissues with sufficient accuracy. This study compares CT and MRCT for pelvic radiotherapy. Methods: CT and multi-contrast MRI acquired using T1- based Dixon, T2 TSE, and PETRA sequences were acquired on an IRBapproved protocol patient. A previously published method was used to create a MRCT image volume by applying fuzzy classification on T1- weighted and calculated water image volumes (air and fluid voxels were excluded using thresholds applied to PETRA and T2-weighted images). The correlation of pelvic bone intensity between CT and MRCT was investigated. Two treatment plans, based on CT and MRCT, were performed to mimic treatment for: (a) pelvic bone metastasis with a 16MV parallel beam arrangement, and (b) gynecological cancer with 6MV volumetric modulated arc therapy (VMAT) using two full arcs. The CT-calculated fluence maps were used to recalculate doses using the MRCT-derived density grid. The dose-volume histograms and dose distributions were compared. Results: Bone intensities in the MRCT volume correlated linearly with CT intensities up to 800 HU (containing 96% of the bone volume), and then decreased with CT intensity increase (4% volume). There was no significant difference in dose distributions between CT- and MRCTbased plans, except for the rectum and bladder, for which the V45 differed by 15% and 9%, respectively. These differences may be attributed to normal and visualized organ movement and volume variations between CT and MR scans. Conclusion: While MRCT had lower bone intensity in highly-dense bone, this did not cause significant dose deviations from CT due to its small percentage of volume. These results indicate that treatment planning using MRCT could generate comparable dose distributions to that using CT, and further demonstrate the feasibility of using MRI-alone to support Radiation Oncology workflow. NIH R01EB016079.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-J-248: Comparative Study of Two Image Registration for Image-Guided Radiation Therapy in Esophageal Cancer

Purpose: Image-guided radiation therapy (IGRT) is one of the major treatment of esophageal cancer. Gray value registration and bone registration are two kinds of image registration, the purpose of this work is to compare which one is more suitable for esophageal cancer patients. Methods: Twenty three esophageal patients were treated by Elekta Synergy, CBCT images were acquired and automatically registered to planning kilovoltage CT scans according to gray value or bone registration. The setup errors were measured in the X, Y and Z axis, respectively. Two kinds of setup errors were analysed by matching T test statistical method. Results: Four hundred and five groups of CBCT images were available and the systematic and random setup errors (cm) in X, Y, Z directions were 0.35, 0.63, 0.29 and 0.31, 0.53, 0.21 with gray value registration, while 0.37, 0.64, 0.26 and 0.32, 0.55, 0.20 with bone registration, respectively. Compared with bone registration and gray value registration, the setup errors in X and Z axis have significant differences. In Y axis, both measurement comparison results of T value is 0.256 (P value > 0.05); In X axis, the T value is 5.287(P value < 0.05); In Z axis, the T value is −5.138 (P value < 0.05). Conclusion: Gray value registration is recommended in image-guided radiotherapy for esophageal cancer and the other thoracic tumors. Manual registration could be applied when it is necessary. Bone registration is more suitable for the head tumor and pelvic tumor department where composed of redundant interconnected and immobile bone tissue.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-T-39: Analyses of Plan Quality Using Different Gantry Rotation Time On Volumetric Modulated Arc Therapy in Rectal Carcinoma

Purpose: To compare plan quality of volumetric modulated arc radiotherapy (VMAT) using different gantry rotation times. Methods: In ten rectal carcinoma patients, plans with different gantry rotation times were designed by Oncentra4.3 planning system, each of them was optimized by experienced planners using almost similar parameters and dose constraints except the different gantry rotation time. The gantry rotation time was increased from 30s to 150s by step of 30(30s, 60s, 90s, 120s, and 150s). Plans (VMAT30s, VMAT60s, VMAT90s, VMAT120s and VMAT150s) were normalized so that at least 95% of PTV would receive the prescription dose 50 Gray in 25 fractions. Dose-volume histograms and isodose distributions were evaluated. Conformity indices (CI), homogeneous indices (HI), monitor units (MUs), delivery time were also compared. Results: As the increasing of gantry rotation time, VMAT150s provided comparable organs at risk sparing and better target coverage and conformity than VMAT30s. In the normal tissue such as bladder and femurs, the VMAT plans show almost the same V30 and Dmean for them compared with IMRT plans, meanwhile the conformity indices (CI) was better than IMRT plans(p=0.021). However, there was no significant different among the VMAT60s, VMAT90s, VMAT120s and VMAT150s (p=0.054). VMAT150s increased delivery time and monitor units in plans without improving plan quality compared to VMAT60s, VMAT90s and VMAT120s. Conclusion: VMAT60s, VMAT90s, VMAT120s and VMAT150s achieved comparable treatment plans in rectal carcinoma. Slower gantry movement in VMAT150s only improves slight improvement than the others.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-T-366: Clinical Implementation of MR-Guided Vaginal Cylinder Brachytherapy

Purpose: To evaluate the accuracy of MR-based vaginal brachytherapy source localization using an in-house MR-visible marker versus the alignment of an applicator model to MR images. Methods: Three consecutive patients undergoing vaginal HDR brachytherapy with a plastic cylinder were scanned with both CT and MRI (including T1- and T2- weighted images). An MR-visible source localization marker, consisting of a sealed thin catheter filled with either water (for T2 contrast) or Gd-doped water (for T1 contrast), was assembled shortly before scanning. Clinically, the applicator channel was digitized on CT with an x-ray marker. To evaluate the efficacy of MR-based applicator reconstruction, each MR image volume was aligned locally to the CT images based on the region containing the cylinder. Applicator digitization was performed on the MR images using (1) the MR visible marker and (2) alignment of an applicator surface model from Varian's Brachytherapy Planning software to the MRI images. Resulting source positions were compared with the original CT digitization. Results: Although the source path was visualized by the MR marker, the applicator tip proved difficult to identify due to challenges in achieving a watertight seal. This resulted in observed displacements of the catheter tip, at times >1cm. Deviations between the central source positions identified via aligning the applicator surface model to MR and using the xray marker on CT ranged from 0.07 – 0.19 cm and 0.07 – 0.20 cm on T1- weighted and T2-weighted images, respectively. Conclusion: Based on the current study, aligning the applicator model to MRI provides a practical, current approach to perform MR-based brachytherapy planning. Further study is needed to produce catheters with reliably and reproducibly identifiable tips. Attempts are being made to improve catheter seals, as well as to increase the viscosity of the contrast material to decrease fluid mobility inside the catheter.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-T-575: Isocenter Shifts in Treatment Planning and Its Clinical Implications

Purpose: To investigate causes of isocenter shifts in treatment planning and its clinical impact on patient treatment efficiency and safety. Methods/Materials: Treatment planning data of 340 patients under treatment over 8 weeks period were gathered to identify isocenter shifts according to site of the treatment, types of treatment plan or types of the machine used. Treatment plans included inversed and forward IMRT, as well as 3D plans. Treatment sites included pelvis, chest, abdomen, breasts, head and necks and extremities. Re-planning were performed without the isocenter shift for pelvis and chest plans, the dosimetric parameters such as PTV coverage, and dose sparing of OARs of these plans were analyzed and compared. Results/Discussions: Results showed that the isocenter shift was always necessary for some of sites such as breasts, two or more distinctive PTVs, or special cases such as large PTV treated with enhanced dynamic wedge. Many other cases, the re-planning results indicated 53% of the plans that the same quality of the plan can be achieved without the shift of the isocenter. Repositioning patients on a daily basis demanded unambiguous instructions for therapists for patient setups, and additional time to perform the shifts before treatment. Opportunities for error propagation exist during the communication and hand-over of such plans. Conclusion: Isocenter shifts demanded unambiguous instructions and times for therapists for daily patient setups, therefore it impacted both safety and efficiency of the patient treatment. Based on the analysis, the isocenter shifts were unavoidable for cases such as treatment of multiple sites, overcoming limitations of treatment machines, and/or sometime better dosimetry. However, we found many initially proposed shifts may have been eliminated either by careful planning or by improved CT simulation process such as detailed review of the images and localization of the PTV during simulation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-T-580: Comparison of Cervical Carcinoma IMRT Plans From Four Commercial Treatment Planning Systems (TPS)

Purpose: Different treatment planning systems (TPS) use different treatment optimization and leaf sequencing algorithms. This work compares cervical carcinoma IMRT plans optimized with four commercial TPSs to investigate the plan quality in terms of target conformity and delivery efficiency. Methods: Five cervical carcinoma cases were planned with the Corvus, Monaco, Pinnacle and Xio TPSs by experienced planners using appropriate optimization parameters and dose constraints to meet the clinical acceptance criteria. Plans were normalized for at least 95% of PTV to receive the prescription dose (Dp). Dose-volume histograms and isodose distributions were compared. Other quantities such as Dmin(the minimum dose received by 99% of GTV/PTV), Dmax(the maximum dose received by 1% of GTV/PTV), D100, D95, D90, V110%, V105%, V100% (the volume of GTV/PTV receiving 110%, 105%, 100% of Dp), conformity index(CI), homogeneity index (HI), the volume of receiving 40Gy and 50 Gy to rectum (V40,V50) ; the volume of receiving 30Gy and 50 Gy to bladder (V30,V50) were evaluated. Total segments and MUs were also compared. Results: While all plans meet target dose specifications and normal tissue constraints, the maximum GTVCI of Pinnacle plans was up to 0.74 and the minimum of Corvus plans was only 0.21, these four TPSs PTVCI had significant difference. The GTVHI and PTVHI of Pinnacle plans are all very low and show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans require significantly less segments and MUs to deliver than the other plans. Conclusion: To deliver on a Varian linear-accelerator, the Pinnacle plans show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans have faster beam delivery.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-T-592: Relationship Between Dose of Distribution and Area of Segment Fields Among Different Intensity-Modulated Radiotherapy Planning in Cervix Cancer

Purpose: In premise of uninfluenced to dose distribution of tumor target and organ at risk(OAR) in cervical cancer,area of segment fields was changed to increase efficacy and optimize treatment method by designing different plan of intensity modulated radiotherapy(IMRT). Methods: 12 cases of cervical cancer were confirmed in pathology and treated with step and shoot IMRT. Dose of PTV was 50Gy/25fractions. Every patient was designed 9 treatment plans of IMRT by Pinnacle 8.0m planning system,each plan was used with 9 beams of uniform distribution and fixing incidence direction(200°,240°,280°,320°,0°,40°,80°,120°and 160°respectively),and designed for delivery on Elekta Synergy linear accelerator. All plans were optimized with the direct machine parameter optimization(DMPO) algorithm using the same set of optimization objectives. Number of maximum segment field was defined at 80 and minimum MU in each segment was 5MU,and minimal segment area was 2*1cm{sup 2},2*2cm{sup 2},3*3cm{sup 2},4*4cm{sup 2},5*5cm{sup 2},6*6cm{sup 2},7*7cm{sup 2},8*8cm{sup 2}and 9*9cm{sup 2},respectively.Coverage,homogeneity and conformity of PTV,sparing of OAR, MU and number of segment were compared. Results: In this group, mean volume of PTV was 916.8±228.7 cm{sup 3}. Compared with the area of minimal segment field increased from 2*1cm{sup 2} to 9*9 cm{sup 2},the number of mean MU was decreased from 1405±170 to 490±47 and the number of segment field was reduced from 76±4 to 39±7 respectively(p<0.05). When the limit of minimal segment area was increased from 2*1cm{sup 2} to 7*7 cm{sup 2},dose distribution of PTV,OAR,CI,HI and V{sub 2} {sub 3} were not different (p>0.05),but when the minimal segment area was 8*8 cm{sup 2} and 9*9 cm{sup 2},they were changed compared with 7*7 cm{sup 2} and below(p<0.05). Conclusion: The minimal segment field of IMRT plan designed by Pinnacle 8.0m planning system in cervical carcinoma should be enlarge reasonably and minimal segment area of 7*7 cm{sup 2} was recommend.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-T-608: Performance Comparison of Four Commercial Treatment Planning Systems Applied to Intensity-Modulated Radiotherapy

Purpose: To compare the performances of four commercial treatment planning systems (TPS) used for the intensity-modulated radiotherapy (IMRT). Methods: Ten patients of nasopharyngeal (4 cases), esophageal (3 cases) and cervical (3 cases) cancer were randomly selected from a 3-month IMRT plan pool at one radiotherapy center. For each patient, four IMRT plans were newly generated by using four commercial TPS (Corvus, Monaco, Pinnacle and Xio), and then verified with Matrixx (two-dimensional array/IBA Company) on Varian23EX accelerator. A pass rate (PR) calculated from the Gamma index by OminiPro IMRT 1.5 software was evaluated at four plan verification standards (1%/1mm, 2%/2mm, 3%/3mm, 4%/4mm and 5%/5mm) for each treatment plan. Overall and multiple pairwise comparisons of PRs were statistically conducted by analysis of covariance (ANOVA) F and LSD tests among four TPSs. Results: Overall significant (p>0.05) differences of PRs were found among four TPSs with F test values of 3.8 (p=0.02), 21.1(>0.01), 14.0 (>0.01), 8.3(>0.01) at standards of 1%/1mm to 4%/4mm respectively, except at 5%/5mm standard with 2.6 (p=0.06). All means (standard deviation) of PRs at 3%/3mm of 94.3 ± 3.3 (Corvus), 98.8 ± 0.8 (Monaco), 97.5± 1.7 (Pinnacle), 98.4 ± 1.0 (Xio) were above 90% and met clinical requirement. Multiple pairwise comparisons had not demonstrated a consistent low or high pattern on either TPS. Conclusion: Matrixx dose verification results show that the validation pass rates of Monaco and Xio plans are relatively higher than those of the other two; Pinnacle plan shows slight higher pass rate than Corvus plan; lowest pass rate was achieved by the Corvus plan among these four kinds of TPS.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Structure and permeation mechanism of a mammalian urea transporter

As an adaptation to infrequent access to water, terrestrial mammals produce urine that is hyperosmotic to plasma. To prevent osmotic diuresis by the large quantity of urea generated by protein catabolism, the kidney epithelia contain facilitative urea transporters (UTs) that allow rapid equilibration between the urinary space and the hyperosmotic interstitium. Here we report the first X-ray crystal structure of a mammalian UT, UT-B, at a resolution of 2.36 {angstrom}. UT-B is a homotrimer and each protomer contains a urea conduction pore with a narrow selectivity filter. Structural analyses and molecular dynamics simulations showed that the selectivity filter has two urea binding sites separated by an approximately 5.0 kcal/mol energy barrier. Functional studies showed that the rate of urea conduction in UT-B is increased by hypoosmotic stress, and that the site of osmoregulation coincides with the location of the energy barrier.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

ANALYSIS OF THE EARLY-TIME OPTICAL SPECTRA OF SN 2011fe IN M101

The nearby Type Ia supernova (SN Ia) SN 2011fe in M101 (cz = 241 km s{sup -1}) provides a unique opportunity to study the early evolution of a 'normal' SN Ia, its compositional structure, and its elusive progenitor system. We present 18 high signal-to-noise spectra of SN 2011fe during its first month beginning 1.2 days post-explosion and with an average cadence of 1.8 days. This gives a clear picture of how various line-forming species are distributed within the outer layers of the ejecta, including that of unburned material (C+O). We follow the evolution of C II absorption features until they diminish near maximum light, showing overlapping regions of burned and unburned material between ejection velocities of 10,000 and 16,000 km s{sup -1}. This supports the notion that incomplete burning, in addition to progenitor scenarios, is a relevant source of spectroscopic diversity among SNe Ia. The observed evolution of the highly Doppler-shifted O I {lambda}7774 absorption features detected within 5 days post-explosion indicates the presence of O I with expansion velocities from 11,500 to 21,000 km s{sup -1}. The fact that some O I is present above C II suggests that SN 2011fe may have had an appreciable amount of unburned oxygen within the outer layers of the ejecta.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2012

Performance and operation of advanced superconducting electron cyclotron resonance ion source SECRAL at 24 GHz

SECRAL (superconducting ECR ion source with advanced design in Lanzhou) ion source has been in routine operation for Heavy Ion Research Facility in Lanzhou (HIRFL) accelerator complex since May 2007. To further enhance the SECRAL performance in order to satisfy the increasing demand for intensive highly charged ion beams, 3-5 kW high power 24 GHz single frequency and 24 GHz +18 GHz double frequency with an aluminum plasma chamber were tested, and some exciting results were produced with quite a few new record highly charged ion beam intensities, such as {sup 129}Xe{sup 35+} of 64 e{mu}A, {sup 129}Xe{sup 42+} of 3 e{mu}A, {sup 209}Bi{sup 41+} of 50 e{mu}A, {sup 209}Bi{sup 50+} of 4.3 e{mu}A and {sup 209}Bi{sup 54+} of 0.2 e{mu}A. In most cases SECRAL is operated at 18 GHz to deliver highly charged heavy ion beams for the HIRFL accelerator, only for those very high charge states and very heavy ion beams such as {sup 209}Bi{sup 36+} and {sup 209}Bi{sup 41+}, SECRAL has been operated at 24 GHz. The total operation beam time provided by SECRAL up to July 2011 has exceeded 7720 hours. In this paper, the latest performance, development, and operation status of SECRAL ion source are presented. The latest results and reliable long-term operation for the HIRFL accelerator have demonstrated that SECRAL performance for production of highly charged heavy ion beams remains improving at higher RF power with optimized tuning.

43 PARTICLE ACCELERATORS↗
DOE OSTI2012

Development of DRAGON electron cyclotron resonance ion source at Institute of Modern Physics

A new room temperature electron cyclotron resonance (ECR) ion source, DRAGON, is under construction at IMP. DRAGON is designed to operate at microwaves of frequencies of 14.5-18 GHz. Its axial solenoid coils are cooled with evaporative medium to provide an axial magnetic mirror field of 2.5 T at the injection and 1.4 T at the extraction, respectively. In comparison to other conventional room temperature ECR ion sources, DRAGON has so far the largest bore plasma chamber of inner diameter of 126 mm with maximum radial fields of 1.4-1.5 T produced by a non-Halbach permanent sextupole magnet.

43 PARTICLE ACCELERATORS↗
DOE OSTI2012

A 2.45 GHz electron cyclotron resonance proton ion source and a dual-lens low energy beam transport

The structure and preliminary commissioning results of a new 2.45 GHz ECR proton ion source and a dual-lens low energy beam transport (LEBT) system are presented in this paper. The main magnetic field of the ion source is provided by a set of permanent magnets with two small electro-solenoid magnets at the injection and the extraction to fine tune the magnetic field for better microwave coupling. A 50 keV pulsed proton beam extracted by a three-electrode mechanism passes through the LEBT system of length of 1183 mm. This LEBT consists of a diagnosis chamber, two Glaser lenses, two steering magnets, and a final beam defining cone. A set of inner permanent magnetic rings is embedded in each of the two Glaser lenses to produce a flatter axial-field to reduce the lens aberrations.

43 PARTICLE ACCELERATORS↗
DOE OSTI2012

Study of ion beam transport from the SECRAL electron cyclotron resonance ion source at the Institute of Modern Physics

Ion beam transport from the Superconducting Electron Cyclotron Resonance ion source with Advanced design in Lanzhou (SECRAL) electron cyclotron resonance ion source was studied at the Institute of Modern Physics during 2010. Particle-in-cell simulations and experimental results have shown that both space charge and magnetic aberrations lead to a larger beam envelope and emittance growth. In the existing SECRAL extraction beam line, it has been shown that raising the solenoid lens magnetic field reduces aberrations in the subsequent dipole and results in lower emittance. Detailed beam emittance measurements are presented in this paper.

43 PARTICLE ACCELERATORS↗
DOE OSTI2011

Crystal Structure of a Phosphorylation-coupled Saccharide Transporter

Saccharides have a central role in the nutrition of all living organisms. Whereas several saccharide uptake systems are shared between the different phylogenetic kingdoms, the phosphoenolpyruvate-dependent phosphotransferase system exists almost exclusively in bacteria. This multi-component system includes an integral membrane protein EIIC that transports saccharides and assists in their phosphorylation. Here we present the crystal structure of an EIIC from Bacillus cereus that transports diacetylchitobiose. The EIIC is a homodimer, with an expansive interface formed between the amino-terminal halves of the two protomers. The carboxy-terminal half of each protomer has a large binding pocket that contains a diacetylchitobiose, which is occluded from both sides of the membrane with its site of phosphorylation near the conserved His250 and Glu334 residues. The structure shows the architecture of this important class of transporters, identifies the determinants of substrate binding and phosphorylation, and provides a framework for understanding the mechanism of sugar translocation.

59 BASIC BIOLOGICAL SCIENCES↗