Date Available
7-4-2016
Year of Publication
2014
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy (PhD)
College
Medicine
Department/School/Program
Molecular and Cellular Biochemistry
Advisor
Dr. Craig Vander Kooi
Co-Director of Graduate Studies
Dr. David Rodgers
Abstract
The vascular system is critical for maintaining homeostasis in all vertebrates. Structural studies of Neuropilin (Nrp), an essential angiogenic receptor, have defined its role in regulating angiogenesis, the formation of new vessels from the existing vasculature. Utilizing biochemical and biophysical tools we describe the ability of Nrp to function as a co-receptor for the VEGFR receptor tyrosine kinase. Two families of Nrp-1 ligands, Vascular Endothelial Growth Factor A (VEGF-A) and Semaphorin3F (Sema3F), physically compete for binding to the Nrp-1 b1 domain, and have opposite roles. VEGF-A is a potent pro-angiogenic cytokine while Sema3F is an angiogenesis inhibitor. Using coupled structural and functional studies, we have discovered the basis for potent competitive binding of Sema3F to Nrp1 requires engagement of two distinct binding sites. These data provide a basis for understanding the rational design of novel high affinity Nrp-1 inhibitor.
Recommended Citation
Guo, Hou-Fu, "NEUROPILIN IN THE VASCULAR SYSTEM: MECHANISTIC BASIS OF ANGIOGENESIS" (2014). Theses and Dissertations--Molecular and Cellular Biochemistry. 16.
https://uknowledge.uky.edu/biochem_etds/16
