4rtd
From Proteopedia
Escherichia coli alpha-2-macroglobulin activated by porcine elastase
Structural highlights
FunctionA2MG_ECOLI Protects the bacterial cell from host peptidases (PubMed:18697741, PubMed:26143919, PubMed:26100869). Acts by a 'trapping' mechanism. Cleavage of the bait-region domain by host peptidases leads to a global conformational change, which results in entrapment of the host peptidase and activation of the thioester bond that covalently binds the attacking host peptidase (PubMed:26143919, PubMed:26100869). Trapped peptidases are still active except against very large substrates (PubMed:26100869). May protect the entire periplam, including the lipoproteins anchored to the periplasmic side of the outer membrane, against intruding endopeptidases (PubMed:26100869).[1] [2] [3] Publication Abstract from PubMedBacterial alpha-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli alpha-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli alpha-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli alpha-2-macroglobulin and human alpha-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group. Structure of protease-cleaved Escherichia coli alpha-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment.,Fyfe CD, Grinter R, Josts I, Mosbahi K, Roszak AW, Cogdell RJ, Wall DM, Burchmore RJ, Byron O, Walker D Acta Crystallogr D Biol Crystallogr. 2015 Jul 1;71(Pt 7):1478-86. doi:, 10.1107/S1399004715008548. Epub 2015 Jun 30. PMID:26143919[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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