PDBsum entry 4g1m

Protein binding

PDB id: 4g1m

Contents

Protein chains

929 a.a.

692 a.a.

Ligands

NAG-NAG-BMA-MAN-MAN

NAG-NAG ×9

NAG-NAG-BMA-MAN-MAN-MAN-MAN

NAG-NAG-BMA

NAG ×4

Metals

_NA

_CA ×7

Waters ×106

PDB id:

4g1m

Name:

Protein binding

Title:

Re-refinement of alpha v beta 3 structure

Structure:

Integrin alpha-v. Chain: a. Synonym: vitronectin receptor subunit alpha, integrin alpha-v heavy chain, integrin alpha-v light chain. Engineered: yes. Integrin beta-3. Chain: b. Synonym: platelet membrane glycoprotein iiia, gpiiia. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: itgav, msk8, vnra. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Gene: itgb3, gp3a. Expression_system_taxid: 10029

Resolution:

2.90Å R-factor: 0.182 R-free: 0.233

Authors:

T.A.Springer,L.Mi,J.Zhu

Key ref:

X.Dong et al. (2012). α(V)β(3) integrin crystal structures and their functional implications. Biochemistry, 51, 8814-8828. PubMed id: 23106217

Date:

10-Jul-12 Release date: 12-Dec-12

Protein chain

P06756  (ITAV_HUMAN) -  Integrin alpha-V from Homo sapiens

Seq: 1048 a.a.

Struc: 929 a.a.

Protein chain

P05106  (ITB3_HUMAN) -  Integrin beta-3 from Homo sapiens

Seq: 788 a.a.

Struc: 692 a.a.

Biochemistry 51:8814-8828 (2012)

PubMed id: 23106217

α(V)β(3) integrin crystal structures and their functional implications.

X.Dong, L.Z.Mi, J.Zhu, W.Wang, P.Hu, B.H.Luo, T.A.Springer.

ABSTRACT

Many questions about the significance of structural features of integrin α(V)β(3) with respect to its mechanism of activation remain. We have determined and re-refined crystal structures of the α(V)β(3) ectodomain linked to C-terminal coiled coils (α(V)β(3)-AB) and four transmembrane (TM) residues in each subunit (α(V)β(3)-1TM), respectively. The α(V) and β(3) subunits with four and eight extracellular domains, respectively, are bent at knees between the integrin headpiece and lower legs, and the headpiece has the closed, low-affinity conformation. The structures differ in the occupancy of three metal-binding sites in the βI domain. Occupancy appears to be related to the pH of crystallization, rather than to the physiologic regulation of ligand binding at the central, metal ion-dependent adhesion site. No electron density was observed for TM residues and much of the α(V) linker. α(V)β(3)-AB and α(V)β(3)-1TM demonstrate flexibility in the linker between their extracellular and TM domains, rather than the previously proposed rigid linkage. A previously postulated interface between the α(V) and β(3) subunits at their knees was also not supported, because it lacks high-quality density, required rebuilding in α(V)β(3)-1TM, and differed markedly between α(V)β(3)-1TM and α(V)β(3)-AB. Together with the variation in domain-domain orientation within their bent ectodomains between α(V)β(3)-AB and α(V)β(3)-1TM, these findings are compatible with the requirement for large structural changes, such as extension at the knees and headpiece opening, in conveying activation signals between the extracellular ligand-binding site and the cytoplasm.