4d90
Crystal Structure of Del-1 EGF domainsCrystal Structure of Del-1 EGF domains
Structural highlights
FunctionEDIL3_HUMAN Promotes adhesion of endothelial cells through interaction with the alpha-v/beta-3 integrin receptor. Inhibits formation of vascular-like structures. May be involved in regulation of vascular morphogenesis of remodeling in embryonic development. Publication Abstract from PubMedDevelopmental endothelial cell locus-1 (Del-1) glycoprotein is secreted by endothelial cells and a subset of macrophages. Del-1 plays a regulatory role in vascular remodeling and functions in innate immunity through interaction with integrin alpha(V)beta(3). Del-1 contains 3 epidermal growth factor (EGF)-like repeats and 2 discoidin-like domains. An Arg-Gly-Asp (RGD) motif in the second EGF domain (EGF2) mediates adhesion by endothelial cells and phagocytes. We report the crystal structure of its 3 EGF domains. The RGD motif of EGF2 forms a type II' beta turn at the tip of a long protruding loop, dubbed the RGD finger. Whereas EGF2 and EGF3 constitute a rigid rod via an interdomain calcium ion binding site, the long linker between EGF1 and EGF2 lends considerable flexibility to EGF1. Two unique O-linked glycans and 1 N-linked glycan locate to the opposite side of EGF2 from the RGD motif. These structural features favor integrin binding of the RGD finger. Mutagenesis data confirm the importance of having the RGD motif at the tip of the RGD finger. A database search for EGF domain sequences shows that this RGD finger is likely an evolutionary insertion and unique to the EGF domain of Del-1 and its homologue milk fat globule-EGF 8.-Schurpf, T., Chen, Q., Liu, J., Wang, R., Springer, T. A., Wang, J. The RGD finger of Del-1 is a unique structural feature critical for integrin binding. The RGD finger of Del-1 is a unique structural feature critical for integrin binding.,Schurpf T, Chen Q, Liu JH, Wang R, Springer TA, Wang JH FASEB J. 2012 May 17. PMID:22601780[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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