1pt6

From Proteopedia

Revision as of 14:41, 15 February 2008

I domain from human integrin alpha1-beta1

Overview

Integrin alpha(1)beta(1) is one of four collagen-binding integrins in, humans. Collagens bind to the alphaI domain and in the case of alpha(2)I, collagen binding is competitively inhibited by peptides containing the, RKKH sequence and derived from the metalloproteinase jararhagin of snake, venom from Bothrops jararaca. In alpha(2)I, these peptides bind near the, metal ion-dependent adhesion site (MIDAS), where a collagen (I)-like, peptide is known to bind; magnesium is required for binding. Published, structures of the ligand-bound "open" conformation of alpha(2)I differs, significantly from the "closed" conformation seen in the structure of, apo-alpha(2)I near MIDAS. Here we show that two peptides, CTRKKHDC and, CARKKHDC, derived from jararhagin also bind to alpha(1)I and competitively, inhibit collagen I binding. Furthermore, calorimetric and fluorimetric, measurements show that the structure of the complex of alpha(1)I with, Mg(2+) and CTRKKHDC differs from structure in the absence of peptide. A, comparison of the x-ray structure of apo-alpha(1)I ("closed" conformation), and a model structure of the alpha(1)I ("open" conformation) based on the, closely related structure of alpha(2)I reveals that the binding site is, partially blocked to ligands by Glu(255) and Tyr(285) in the "closed", structure, whereas in the "open" structure helix C is unwound and these, residues are shifted, and the "RKKH" peptides fit well when docked. The, "open" conformation of alpha(2)I resulting from binding a collagen, (I)-like peptide leads to exposure of hydrophobic surface, also seen in, the model of alpha(1)I and shown experimentally for alpha(1)I using a, fluorescent hydrophobic probe.

About this Structure

1PT6 is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.

Reference

Jararhagin-derived RKKH peptides induce structural changes in alpha1I domain of human integrin alpha1beta1., Nymalm Y, Puranen JS, Nyholm TK, Kapyla J, Kidron H, Pentikainen OT, Airenne TT, Heino J, Slotte JP, Johnson MS, Salminen TA, J Biol Chem. 2004 Feb 27;279(9):7962-70. Epub 2003 Dec 4. PMID:14660600

Page seeded by OCA on Fri Feb 15 16:41:22 2008