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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001646-29
Application #
8363564
Study Section
Special Emphasis Panel (ZRG1-BCMB-E (40))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
29
Fiscal Year
2011
Total Cost
$5,845
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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