PDBsum entry 1qcy

Cell adhesion

PDB id: 1qcy

Contents

Protein chain

193 a.a. *

Metals

_MG

Waters ×94

* Residue conservation analysis

PDB id:

1qcy

Name:

Cell adhesion

Title:

The crystal structure of the i-domain of human integrin alpha1beta1

Structure:

I-domain of integrin alpha1beta1. Chain: a. Fragment: fragment, i-domain of human integrin a1b1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.30Å R-factor: 0.200 R-free: 0.258

Authors:

J.A.Kankare,T.A.Salminen,Y.Nymalm,J.Kaepylae,J.Heino,M.S.Johnson

Key ref:

Y.Nymalm et al. (2004). Jararhagin-derived RKKH peptides induce structural changes in alpha1I domain of human integrin alpha1beta1. J Biol Chem, 279, 7962-7970. PubMed id: 14660600 DOI: 10.1074/jbc.M312912200

Date:

12-May-99 Release date: 02-Sep-03

Protein chain

P56199  (ITA1_HUMAN) -  Integrin alpha-1 from Homo sapiens

Seq: 1179 a.a.

Struc: 193 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1074/jbc.M312912200

J Biol Chem 279:7962-7970 (2004)

PubMed id: 14660600

Jararhagin-derived RKKH peptides induce structural changes in alpha1I domain of human integrin alpha1beta1.

Y.Nymalm, J.S.Puranen, T.K.Nyholm, J.Käpylä, H.Kidron, O.T.Pentikäinen, T.T.Airenne, J.Heino, J.P.Slotte, M.S.Johnson, T.A.Salminen.

ABSTRACT

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.

Selected figure(s)

Figure 6.
FIG. 6. Conformational changes proposed to occur in [1]I. Comparison of "closed" (x-ray structure) (A) and "open" (model structure) conformations of [1]I (B). Tyr285 and Trp158 are shown, and the metal ion at MIDAS is colored pink. Helix 6 and helix C are colored red, whereas helix 7 is colored blue. The model structure of the "open" conformation is based on the close similarity with [2]I, whose structure in the "open" form is known. Figs. 6, 7, 8 were prepared using Molscript 2.1.2 (70), Raster3D 2.7b (49), and GIMP 1.3.20 (available on the World Wide Web at www.gimp.org). Molecular surfaces were made using Bodil.2

Figure 8.
FIG. 8. In comparison with the "closed" conformation, the "open" conformation exposes localized patches of hydrophobic surface. A, [1]I, "closed" conformation. B, model of [1]I with bound CTRKKHDC peptide, "open" conformation. C, [2]I, "closed" conformation. D, [2]I with bound collagen (I)-like peptide, "open" conformation. Residues contributing to the patches are labeled, and their hydrophobic atoms were colored in gray.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 7962-7970) copyright 2004.

Figures were selected by the author.