3SH4

Laminin G like domain 3 from human perlecan

Summary for 3SH4

• Entry DOI: 10.2210/pdb3sh4/pdb
• Related: 3SH5
• Descriptor: LG3 peptide (2 entities in total)
• Functional Keywords: actin disassambly, integrin alpha12 beta1, metal binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space, extracellular matrix, basement membrane: P98160
• Total number of polymer chains: 1
• Total formula weight: 20571.80

Authors

Van Le, B.,Kim, K.K. (deposition date: 2011-06-15, release date: 2011-12-14, Last modification date: 2024-11-06)

Primary citation

Van Le, B.,Kim, H.,Choi, J.,Kim, J.H.,Hahn, M.J.,Lee, C.,Kim, K.K.,Hwang, H.Y.
Crystal Structure of the LG3 Domain of Endorepellin, an Angiogenesis Inhibitor.
J.Mol.Biol., 414:231-242, 2011

PubMed 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.

PubMed: 21996443
DOI: 10.1016/j.jmb.2011.09.048

Experimental method

X-RAY DIFFRACTION (1.5 Å)