6BE6

ADAM10 Extracellular Domain

6BE6 の概要

• エントリーDOI: 10.2210/pdb6be6/pdb
• 関連するPDBエントリー: 6BDZ
• 分子名称: Disintegrin and metalloproteinase domain-containing protein 10, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• 機能のキーワード: adam10, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 203797.87

構造登録者

Seegar, T.C.M. (登録日: 2017-10-24, 公開日: 2017-12-27, 最終更新日: 2024-12-25)

主引用文献

Seegar, T.C.M.,Killingsworth, L.B.,Saha, N.,Meyer, P.A.,Patra, D.,Zimmerman, B.,Janes, P.W.,Rubinstein, E.,Nikolov, D.B.,Skiniotis, G.,Kruse, A.C.,Blacklow, S.C.
Structural Basis for Regulated Proteolysis by the alpha-Secretase ADAM10.
Cell, 171:1638-1648.e7, 2017

PubMed Abstract: Cleavage of membrane-anchored proteins by ADAM (a disintegrin and metalloproteinase) endopeptidases plays a key role in a wide variety of biological signal transduction and protein turnover processes. Among ADAM family members, ADAM10 stands out as particularly important because it is both responsible for regulated proteolysis of Notch receptors and catalyzes the non-amyloidogenic α-secretase cleavage of the Alzheimer's precursor protein (APP). We present here the X-ray crystal structure of the ADAM10 ectodomain, which, together with biochemical and cellular studies, reveals how access to the enzyme active site is regulated. The enzyme adopts an unanticipated architecture in which the C-terminal cysteine-rich domain partially occludes the enzyme active site, preventing unfettered substrate access. Binding of a modulatory antibody to the cysteine-rich domain liberates the catalytic domain from autoinhibition, enhancing enzymatic activity toward a peptide substrate. Together, these studies reveal a mechanism for regulation of ADAM activity and offer a roadmap for its modulation.

PubMed: 29224781
DOI: 10.1016/j.cell.2017.11.014

実験手法

X-RAY DIFFRACTION (2.8 Å)