Crystal Structure of the LG3 Domain of Endorepellin, an Angiogenesis Inhibitor

Title
Crystal Structure of the LG3 Domain of Endorepellin, an Angiogenesis Inhibitor
Authors
V Le B김훈최종근김진한한명준이철주김경규황혜연
Keywords
perlecan; endorepellin; X-ray structure; angiogenesis; laminin-like globular domain
Issue Date
2011-11
Publisher
Journal of molecular biology
Citation
VOL 414, NO 2, 231-242
Abstract
Endorepellin, the C-terminal region of perlecan, inhibits angiogenesis by disrupting actin cytoskeleton and focal adhesions. The C-terminal laminin-like globular domain (LG3) of endorepellin directs most of this antiangiogenic activity. To investigate the angiostatic mechanism and to identify structural determinants, we have solved crystal structures of the LG3 domain in both apo- and calcium-bound forms at resolutions of 1.5 Å and 2.8 Å, respectively. The conserved core has the jellyroll fold characteristic of LG domains. The calcium-induced structural changes seem very restricted, and the calcium binding site appears to be preformed, suggesting that the bound calcium ion, rather than structural rearrangements, contributes to antiangiogenesis. We have identified H4268 on the EF loop as a key residue for the biochemical function of LG3, since its mutation abolishes antiangiogenic activity, and mutant LG3 can no longer form a direct interaction with integrin. Taken together, we propose that these two distinct structural elements contribute to the angiostatic effect of endorepellin.
URI
http://pubs.kist.re.kr/handle/201004/41103
ISSN
0022-2836
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KIST Publication > Article
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