Le, Binh V. Kim, Hun Choi, Jongkeun Kim, Jin-Hahn Hahn, Myong-Joon Lee, Cheolju Kim, Kyeong Kyu Hwang, Hye-Yeon 2024-01-20T16:01:39Z 2024-01-20T16:01:39Z 2021-09-05 2011-11-25 0022-2836 https://pubs.kist.re.kr/handle/201004/129797 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 angstrom and 2.8 angstrom, 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. (C) 2011 Elsevier Ltd. All rights reserved. English ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD C-TERMINAL FRAGMENT ALPHA-DYSTROGLYCAN LAMININ ALPHA-1 BINDING PERLECAN ENDOSTATIN RECEPTOR PROTEIN SITES Crystal Structure of the LG3 Domain of Endorepellin, an Angiogenesis Inhibitor Article 10.1016/j.jmb.2011.09.048 1 JOURNAL OF MOLECULAR BIOLOGY, v.414, no.2, pp.231 - 242 JOURNAL OF MOLECULAR BIOLOGY 414 2 231 242 scie scopus 000298127500006 2-s2.0-81355160213 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article C-TERMINAL FRAGMENT ALPHA-DYSTROGLYCAN LAMININ ALPHA-1 BINDING PERLECAN ENDOSTATIN RECEPTOR PROTEIN SITES perlecan endorepellin X-ray structure angiogenesis laminin-like globular domain