1c9g

Theoretical Model: The protein structure described on this page was determined theoretically, and hence should be interpreted with caution.

"RKKH" PEPTIDES FROM THE SNAKE VENOM METALLOPROTEINASE OF BOTHROPS JARARACA BIND NEAR THE MIDAS SITE OF THE HUMAN INTEGRIN ALPHA2 I-DOMAIN"RKKH" PEPTIDES FROM THE SNAKE VENOM METALLOPROTEINASE OF BOTHROPS JARARACA BIND NEAR THE MIDAS SITE OF THE HUMAN INTEGRIN ALPHA2 I-DOMAIN

Structural highlights For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, PDBsum, ProSAT Publication Abstract from PubMed Integrin alpha(1)beta(1) and alpha(2)beta(1) are the major cellular receptors for collagen, and collagens bind to these integrins at the inserted I-domain in their alpha subunit. We have previously shown that a cyclic peptide derived from the metalloproteinase domain of the snake venom protein jararhagin blocks the collagen-binding function of the alpha(2) I-domain. Here, we have optimized the structure of the peptide and identified the site where the peptide binds to the alpha(2) I-domain. The peptide sequence Arg-Lys-Lys-His is critical for recognition by the I-domain, and five negatively charged residues surrounding the "metal ion-dependent adhesion site" (MIDAS) of the I-domain, when mutated, show significantly impaired binding of the peptide. Removal of helix alphaC, located along one side of the MIDAS and suggested to be involved in collagen-binding in these I-domains, does not affect peptide binding. This study supports the notion that the metalloproteinase initially binds to the alpha(2) I-domain at a location distant from the active site of the protease, thus blocking collagen binding to the adhesion molecule in the vicinity of the MIDAS, while at the same time leaving the active site free to degrade nearby proteins, the closest being the beta(1) subunit of the alpha(2)beta(1) cell-surface integrin itself. "RKKH" peptides from the snake venom metalloproteinase of Bothrops jararaca bind near the metal ion-dependent adhesion site of the human integrin alpha(2) I-domain.,Pentikainen O, Hoffren AM, Ivaska J, Kapyla J, Nyronen T, Heino J, Johnson MS J Biol Chem. 1999 Oct 29;274(44):31493-505. PMID:10531352 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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