7Q61

Structure of TEV conjugated A2ML1 (A2ML1-TC)

7Q61 の概要

• エントリーDOI: 10.2210/pdb7q61/pdb
• EMDBエントリー: 13849
• 分子名称: Alpha-2-macroglobulin-like protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: protease inhibitor, thioester, immune system
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 160851.71

構造登録者

Nielsen, N.S.,Zarantonello, A.,Andersen, G.R. (登録日: 2021-11-05, 公開日: 2022-04-20, 最終更新日: 2025-07-02)

主引用文献

Nielsen, N.S.,Zarantonello, A.,Harwood, S.L.,Jensen, K.T.,Kjoge, K.,Thogersen, I.B.,Schauser, L.,Karlsen, J.L.,Andersen, G.R.,Enghild, J.J.
Cryo-EM structures of human A2ML1 elucidate the protease-inhibitory mechanism of the A2M family.
Nat Commun, 13:3033-3033, 2022

PubMed Abstract: A2ML1 is a monomeric protease inhibitor belonging to the A2M superfamily of protease inhibitors and complement factors. Here, we investigate the protease-inhibitory mechanism of human A2ML1 and determine the structures of its native and protease-cleaved conformations. The functional inhibitory unit of A2ML1 is a monomer that depends on covalent binding of the protease (mediated by A2ML1's thioester) to achieve inhibition. In contrast to the A2M tetramer which traps proteases in two internal chambers formed by four subunits, in protease-cleaved monomeric A2ML1 disordered regions surround the trapped protease and may prevent substrate access. In native A2ML1, the bait region is threaded through a hydrophobic channel, suggesting that disruption of this arrangement by bait region cleavage triggers the extensive conformational changes that result in protease inhibition. Structural comparisons with complement C3/C4 suggest that the A2M superfamily of proteins share this mechanism for the triggering of conformational change occurring upon proteolytic activation.

PubMed: 35641520
DOI: 10.1038/s41467-022-30758-x

実験手法

ELECTRON MICROSCOPY (2.88 Å)