4O02

AlphaVBeta3 integrin in complex with monoclonal antibody FAB fragment.

4O02 の概要

• エントリーDOI: 10.2210/pdb4o02/pdb
• 分子名称: Integrin alpha-V, 2-acetamido-2-deoxy-beta-D-glucopyranose, MANGANESE (II) ION, ... (12 entities in total)
• 機能のキーワード: protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 236044.93

構造登録者

Mahalingam, B.,van Agthoven, J.,Xiong, J.,Arnaout, M.A. (登録日: 2013-12-13, 公開日: 2014-04-02, 最終更新日: 2020-07-29)

主引用文献

Mahalingam, B.,Van Agthoven, J.F.,Xiong, J.P.,Alonso, J.L.,Adair, B.D.,Rui, X.,Anand, S.,Mehrbod, M.,Mofrad, M.R.,Burger, C.,Goodman, S.L.,Arnaout, M.A.
Atomic basis for the species-specific inhibition of alpha V integrins by monoclonal antibody 17E6 is revealed by the crystal structure of alpha V beta 3 ectodomain-17E6 Fab complex.
J.Biol.Chem., 289:13801-13809, 2014

PubMed Abstract: The function-blocking, non-RGD-containing, and primate-specific mouse monoclonal antibody 17E6 binds the αV subfamily of integrins. 17E6 is currently in phase II clinical trials for treating cancer. To elucidate the structural basis of recognition and the molecular mechanism of inhibition, we crystallized αVβ3 ectodomain in complex with the Fab fragment of 17E6. Protein crystals grew in presence of the activating cation Mn(2+). The integrin in the complex and in solution assumed the genuflected conformation. 17E6 Fab bound exclusively to the Propeller domain of the αV subunit. At the core of αV-Fab interface were interactions involving Propeller residues Lys-203 and Gln-145, with the latter accounting for primate specificity. The Propeller residue Asp-150, which normally coordinates Arg of the ligand Arg-Gly-Asp motif, formed contacts with Arg-54 of the Fab that were expected to reduce soluble FN10 binding to cellular αVβ3 complexed with 17E6. This was confirmed in direct binding studies, suggesting that 17E6 is an allosteric inhibitor of αV integrins.

PubMed: 24692540
DOI: 10.1074/jbc.M113.546929

実験手法

X-RAY DIFFRACTION (3.605 Å)