4G1E

Crystal structure of integrin alpha V beta 3 with coil-coiled tag.

Summary for 4G1E

• Entry DOI: 10.2210/pdb4g1e/pdb
• Descriptor: Integrin alpha-V, 2-acetamido-2-deoxy-beta-D-glucopyranose, SULFATE ION, ... (14 entities in total)
• Functional Keywords: protein binding, cell surface receptor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 202768.93

Authors

Dong, X.,Mi, L.,Zhu, J.,Wang, W.,Luo, B.,Springer, T.A. (deposition date: 2012-07-10, release date: 2012-12-12, Last modification date: 2020-07-29)

Primary citation

Dong, X.,Mi, L.Z.,Zhu, J.,Wang, W.,Hu, P.,Luo, B.H.,Springer, T.A.
AlphaV Beta3 Integrin Crystal Structures and their Functional Implications
Biochemistry, 51:8814-8828, 2012

PubMed 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.

PubMed: 23106217
DOI: 10.1021/bi300734n

Experimental method

X-RAY DIFFRACTION (3 Å)