Editors' ChoiceStructural Biology

A Safety Catch on Immune Response

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Science Signaling  04 Jan 2011:
Vol. 4, Issue 154, pp. ec7
DOI: 10.1126/scisignal.4154ec7

The complement system is an integral part of the innate immune system. When triggered, it initiates a cascade that marks intruders for elimination and stimulates immune responses. The key amplification step is cleavage of a complex comprising the complement fragment C3b and factor B (C3bB) by factor D (FD). Forneris et al. now describe the crystal structure of C3bB and its complex with FD. The structures support a mechanism in which membrane-bound C3b stabilizes an open form of factor B (FB) that has its scissile bond accessible. FD binds through a site distant from its catalytic center to the open form of FB, which activates FD. The two conformational equilibria represent a double safety-catch that would allow tight regulation of this immune response pathway.

F. Forneris, D. Ricklin, J. Wu, A. Tzekou, R. S. Wallace, J. D. Lambris, P. Gros, Structures of C3b in complex with factors B and D give insight into complement convertase formation. Science 330, 1816–1820 (2010). [Abstract] [Full Text]