EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Cryo-EM structures show the mechanistic basis of pan-peptidase inhibition by human α-macroglobulin.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 119, Issue 19, Page e2200102119, Year 2022
掲載日	2022年5月10日
著者	Daniel Luque / Theodoros Goulas / Carlos P Mata / Soraia R Mendes / F Xavier Gomis-Rüth / José R Castón /
PubMed 要旨	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 ...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.
リンク	Proc Natl Acad Sci U S A / PubMed:35500114 / PubMed Central
手法	EM (単粒子)
解像度	3.6 - 12.0 Å
構造データ	12747 7o7l EMDB-12747, PDB-7o7l: (h-alpha2M)4 native I 手法: EM (単粒子) / 解像度: 4.5 Å 12748 7o7m EMDB-12748, PDB-7o7m: (h-alpha2M)4 native II 手法: EM (単粒子) / 解像度: 6.6 Å 12750 7o7n EMDB-12750, PDB-7o7n: (h-alpha2M)4 semiactivated I state 手法: EM (単粒子) / 解像度: 7.3 Å 12751 7o7o EMDB-12751, PDB-7o7o: (h-alpha2M)4 semiactivated II state 手法: EM (単粒子) / 解像度: 4.8 Å 12752 7o7p EMDB-12752, PDB-7o7p: (h-alpha2M)4 activated state 手法: EM (単粒子) / 解像度: 4.6 Å 12753 7o7q EMDB-12753, PDB-7o7q: (h-alpha2M)4 trypsin-activated state 手法: EM (単粒子) / 解像度: 3.6 Å 12754 7o7r EMDB-12754, PDB-7o7r: (h-alpha2M)4 plasmin-activated I state 手法: EM (単粒子) / 解像度: 3.9 Å 12755 7o7s EMDB-12755, PDB-7o7s: (h-alpha2M)4 plasmin-activated II state 手法: EM (単粒子) / 解像度: 4.3 Å EMDB-12941: (h-alpha2M)4 transient I state 手法: EM (単粒子) / 解像度: 5.2 Å EMDB-12942: (h-alpha2M)4 transient II state 手法: EM (単粒子) / 解像度: 12.0 Å EMDB-12943: (h-alpha2M)4 transient III state 手法: EM (単粒子) / 解像度: 9.1 Å EMDB-12944: (h-alpha2M)4 transient IV state 手法: EM (単粒子) / 解像度: 9.3 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン
由来	homo sapiens (ヒト) Human (ヒト)
キーワード	PROTEIN BINDING / alpha2-macroglobulin / proteinase / serum proteostasis / hydrolase inhibitor