PDBsum entry 1v7p

Toxin/cell adhesion

PDB id: 1v7p

Contents

Protein chains

134 a.a. *

127 a.a. *

193 a.a. *

Ligands

PO4

NAG

Metals

_CL

_MN

Waters ×463

* Residue conservation analysis

PDB id:

1v7p

Name:

Toxin/cell adhesion

Title:

Structure of ems16-alpha2-i domain complex

Structure:

Ems16 a chain. Chain: a. Fragment: residues 1-134. Synonym: ems16 subunit a. Ems16 b chain. Chain: b. Fragment: residues 1-128. Synonym: ems16 subunit b. Integrin alpha-2.

Source:

Echis multisquamatus. Organism_taxid: 93050. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Hexamer (from PQS)

Resolution:

1.90Å R-factor: 0.188 R-free: 0.235

Authors:

K.Horii,D.Okuda,T.Morita,H.Mizuno

Key ref:

K.Horii et al. (2004). Crystal structure of EMS16 in complex with the integrin alpha2-I domain. J Mol Biol, 341, 519-527. PubMed id: 15276841 DOI: 10.1016/j.jmb.2004.06.036

Date:

19-Dec-03 Release date: 07-Sep-04

Protein chain

Q7T2Q1  (SLA_ECHML) -  Snaclec EMS16 subunit alpha from Echis multisquamatus

Seq: 157 a.a.

Struc: 134 a.a.

Protein chain

Q7T2Q0  (SLB_ECHML) -  Snaclec EMS16 subunit beta from Echis multisquamatus

Seq: 154 a.a.

Struc: 127 a.a.*

Protein chain

P17301  (ITA2_HUMAN) -  Integrin alpha-2 from Homo sapiens

Seq: 1181 a.a.

Struc: 193 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/j.jmb.2004.06.036

J Mol Biol 341:519-527 (2004)

PubMed id: 15276841

Crystal structure of EMS16 in complex with the integrin alpha2-I domain.

K.Horii, D.Okuda, T.Morita, H.Mizuno.

ABSTRACT

Snake venoms contain a number of heterodimeric C-type lectin-like proteins (CLPs) that interact specifically with components of the haemostatic system. EMS16 from the venom of Echis multisquamatus binds to the collagen receptor, integrin alpha2beta1, also known as glycoprotein (GP) Ia/IIa, and specifically inhibits collagen binding. Here we report the crystal structure of EMS16 in complex with recombinant integrin alpha2-I domain that plays a central role in collagen binding. The structure of the complex at 1.9 Angstrom resolution reveals that the collagen-binding site of the alpha2-I domain is covered completely by the bound EMS16. This blockage by EMS16 appears to spatially inhibit collagen binding to the alpha2-I domain. The bound alpha2-I domain adopts a closed conformation, which is seen in the absence of ligand, suggesting that EMS16 stabilizes a closed conformation corresponding to the less active structure of the alpha2-I domain. EMS16 does not directly bind to the manganese ion and residues of the metal ion-dependent adhesion site (MIDAS) of the alpha2-I domain, suggesting that EMS16 may have the potential to bind specifically to the alpha2-I domain in a metal ion-independent fashion.

Selected figure(s)

Figure 1.
Figure 1. Overall structure of the EMS16-a2-I domain complex. (a) Ribbon representation of the EMS16-a2-I domain complex. Two subunits, A and B, of EMS16 and the a2-I domain are color-coded in green, magenta, and cyan, respectively. A manganese ion is shown by a large orange sphere, b strands by curved arrows, and a-helix by helical ribbons. Major secondary structure elements are labeled. The collagen-binding site is shown with a dotted line. (b) Top view of the complex rotated by 90° compared to (a) along the horizontal axis. The glycosylated sugar, GlcNAc, is shown in ball-and-stick representation. The collagen-binding site is shown with a dotted line. (c) Stereo representation of the residues at the interface between subunit A of EMS16 (magenta) and a2-I domain (cyan). Interacting residues between intermoleclues are shown in ball-and-stick representation, and manganese ion as orange sphere. C^a trace tubes are colored similarly for each molecule. Hydrogen bonds are indicated by black doted lines. (d) Stereo representation of the residues at the interface between subunit B of EMS16 (green) and the a2-I domain (cyan). Figures were created with MOLSCRIPT[36.] and Raster3D. [37.]

Figure 2.
Figure 2. Stereo representation of the superposed structural elements of the complexed and uncomplexed molecules. Superposition of the EMS16-bound (cyan, this study), collagen-bound (magenta),[11.] and unliganded (yellow) [10.] a2-I domains. Figure was drawn with ViewerPro 4.2 (Accelrys; http://www.accelrys.com).

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 341, 519-527) copyright 2004.

Figures were selected by an automated process.