STRUCTURAL STUDY OF EPH RECEPTORS

EPH受体的结构研究

• 批准号: 8363564
• 负责人: DIMITAR B NIKOLOV
• 金额: $ 0.58万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363564
• 关键词: Binding; Cells; Complex; Data; Data Collection; Development; Eph Family Receptors; Ephrin-A5; Ephrins; Funding; Grant; Ligands; Molecular; National Center for Research Resources; Oncogenic; Principal Investigator; Process; Research; Research Infrastructure; Resolution; Resources; Signal Transduction; Source; Structure; United States National Institutes of Health; base; cost; improved; inhibitor/antagonist; small molecule

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Eph receptor tyrosine kinases and their ephrin ligands regulate cell navigation during normal and oncogenic development. Signaling of Ephs is initiated in a multistep process leading to the assembly of higher-order signaling clusters that set off bidirectional signaling in interacting cells. However, the structural and mechanistic details of this assembly remained undefined. We request Chess A1 beamtine to determine the structures of the complete EphA4 ectodomain and complexes with ephrin-A5 as the base unit of an Eph cluster. We have also obtained crystals of EphA4 bound to a small-molecule inhibitor which we will collect data on. Previous crystallographic data collection on our EphA4 and EphA4/ephrin-A5 crystals reveal diffraction to approximately 4.0 A. We have now, though, improved the size and quality of the crystals, and expect that we will be able to collect higher-resolution data. The structures will be determined using molecular replacement with known structures of fragments of other Eph receptors which share significant sequence identity (50%) to EphA4. We have also previously determined the structure of unbound ephrin-A5.

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