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|2qqk, resolution 2.75Å ()|
|Gene:||NRP2, VEGF165R2 (Homo sapiens)|
|Related:||2qqi, 2qqj, 2qql, 2qqm, 2qqn, 2qqo|
Neuropilin-2 a1a2b1b2 Domains in Complex with a Semaphorin-Blocking Fab
Neuropilins (Nrps) are co-receptors for class 3 semaphorins and vascular endothelial growth factors and important for the development of the nervous system and the vasculature. The extracellular portion of Nrp is composed of two domains that are essential for semaphorin binding (a1a2), two domains necessary for VEGF binding (b1b2), and one domain critical for receptor dimerization (c). We report several crystal structures of Nrp1 and Nrp2 fragments alone and in complex with antibodies that selectively block either semaphorin or vascular endothelial growth factor (VEGF) binding. In these structures, Nrps adopt an unexpected domain arrangement in which the a2, b1, and b2 domains form a tightly packed core that is only loosely connected to the a1 domain. The locations of the antibody epitopes together with in vitro experiments indicate that VEGF and semaphorin do not directly compete for Nrp binding. Based upon our structural and functional data, we propose possible models for ligand binding to neuropilins.
Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding., Appleton BA, Wu P, Maloney J, Yin J, Liang WC, Stawicki S, Mortara K, Bowman KK, Elliott JM, Desmarais W, Bazan JF, Bagri A, Tessier-Lavigne M, Koch AW, Wu Y, Watts RJ, Wiesmann C, EMBO J. 2007 Nov 28;26(23):4902-12. Epub 2007 Nov 8. PMID:17989695
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[NRP2_HUMAN] High affinity receptor for semaphorins 3C, 3F, VEGF-165 and VEGF-145 isoforms of VEGF, and the PLGF-2 isoform of PGF.
About this Structure
- Appleton BA, Wu P, Maloney J, Yin J, Liang WC, Stawicki S, Mortara K, Bowman KK, Elliott JM, Desmarais W, Bazan JF, Bagri A, Tessier-Lavigne M, Koch AW, Wu Y, Watts RJ, Wiesmann C. Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding. EMBO J. 2007 Nov 28;26(23):4902-12. Epub 2007 Nov 8. PMID:17989695