7O7M

(h-alpha2M)4 native II

7O7M の概要

• エントリーDOI: 10.2210/pdb7o7m/pdb
• EMDBエントリー: 12748
• 分子名称: Alpha-2-macroglobulin, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: alpha2-macroglobulin, proteinase, serum proteostasis, hydrolase inhibitor, protein binding
• 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: 663130.91

構造登録者

Luque, D.,Goulas, T.,Mata, C.P.,Mendes, S.R.,Gomis-Ruth, F.X.,Caston, J.R. (登録日: 2021-04-13, 公開日: 2022-04-13, 最終更新日: 2024-10-23)

主引用文献

Luque, D.,Goulas, T.,Mata, C.P.,Mendes, S.R.,Gomis-Ruth, F.X.,Caston, J.R.
Cryo-EM structures show the mechanistic basis of pan-peptidase inhibition by human alpha 2 -macroglobulin.
Proc.Natl.Acad.Sci.USA, 119:e2200102119-e2200102119, 2022

PubMed Abstract: Human α2-macroglobulin (hα2M) is a multidomain protein with a plethora of essential functions, including transport of signaling molecules and endopeptidase inhibition in innate immunity. Here, we dissected the molecular mechanism of the inhibitory function of the ∼720-kDa hα2M tetramer through eight cryo–electron microscopy (cryo-EM) structures of complexes from human plasma. In the native complex, the hα2M subunits are organized in two flexible modules in expanded conformation, which enclose a highly porous cavity in which the proteolytic activity of circulating plasma proteins is tested. Cleavage of bait regions exposed inside the cavity triggers rearrangement to a compact conformation, which closes openings and entraps the prey proteinase. After the expanded-to-compact transition, which occurs independently in the four subunits, the reactive thioester bond triggers covalent linking of the proteinase, and the receptor-binding domain is exposed on the tetramer surface for receptor-mediated clearance from circulation. These results depict the molecular mechanism of a unique suicidal inhibitory trap.

PubMed: 35500114
DOI: 10.1073/pnas.2200102119

実験手法

ELECTRON MICROSCOPY (6.6 Å)