conformational states of a bacterial α2-macroglobulin resemble those of human complement c3构象状态的细菌α2-macroglobulin类似人类补体c3.pdfVIP

Conformational States of a Bacterial a -Macroglobulin 2 Resemble Those of Human Complement C3 David Neves1,2,3, Leandro F. Estrozi1,2,3, Viviana Job1,2,3, Frank Gabel1,2,3, Guy Schoehn1,2,3,4, ´ 1,2,3* Andrea Dessen ´ ` 1 Institut de Biologie Structurale (IBS), Universite Grenoble I, Grenoble, France, 2 Centre National de la Recherche Scientifique (CNRS), Grenoble, France, 3 Commissariat a l’Energie Atomique (CEA), Grenoble, France, 4 Unit for Virus Host Cell Interactions UMI 3265 (UJF-EMBL-CNRS), Grenoble, France Abstract a macroglobulins (a Ms) are broad-spectrum protease inhibitors that play essential roles in the innate immune system of 2 2 eukaryotic species. These large, multi-domain proteins are characterized by a broad-spectrum bait region and an internal thioester, which, upon cleavage, becomes covalently associated to the target protease, allowing its entrapment by a large conformational modification. Notably, a2Ms are part of a larger protein superfamily that includes proteins of the complement system, such as C3, a multi-domain macromolecule which is also characterized by an internal thioester- carrying domain and whose activation represents the pivotal step in the complement cascade. Recently, a2M/C3-like genes were identified in a large number of bacterial genomes, and the Escherichia coli a2M homolog (ECAM) was shown to be activated by proteases. In this work, we have structurally characterized ECAM