7Q62
Structure of TEV cleaved A2ML1 dimer (A2ML1-TT dimer)
Summary for 7Q62
| Entry DOI | 10.2210/pdb7q62/pdb |
| EMDB information | 13850 |
| Descriptor | Alpha-2-macroglobulin-like protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total) |
| Functional Keywords | protease inhibitor, thioester, immune system |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 320890.64 |
| Authors | Nielsen, N.S.,Zarantonello, A.,Andersen, G.R. (deposition date: 2021-11-05, release date: 2022-04-20, Last modification date: 2022-11-02) |
| Primary citation | 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 Cited by 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: 35641520DOI: 10.1038/s41467-022-30758-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.18 Å) |
Structure validation
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