Molecular basis for complement recognition and inhibition determined by crystallographic studies of the staphylococcal complement inhibitor (SCIN) bound to C3c and C3b.

Journal of Molecular Biology
Brandon L GarciaBrian V Geisbrecht

Abstract

The human complement system plays an essential role in innate and adaptive immunity by marking and eliminating microbial intruders. Activation of complement on foreign surfaces results in proteolytic cleavage of complement component 3 (C3) into the potent opsonin C3b, which triggers a variety of immune responses and participates in a self-amplification loop mediated by a multi-protein assembly known as the C3 convertase. The human pathogen Staphylococcus aureus has evolved a sophisticated and potent complement evasion strategy, which is predicated upon an arsenal of potent inhibitory proteins. One of these, the staphylococcal complement inhibitor (SCIN), acts at the level of the C3 convertase (C3bBb) and impairs downstream complement function by trapping the convertase in a stable but inactive state. Previously, we have shown that SCIN binds C3b directly and competitively inhibits binding of human factor H and, to a lesser degree, that of factor B to C3b. Here, we report the co-crystal structures of SCIN bound to C3b and C3c at 7.5 and 3.5 A limiting resolution, respectively, and show that SCIN binds a critical functional area on C3b. Most significantly, the SCIN binding site sterically occludes the binding sites of both factor...Continue Reading

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Citations

Apr 14, 2012·The Journal of Biological Chemistry·Alexander E AleshinRobert C Liddington
Dec 13, 2012·The Journal of Biological Chemistry·Brandon L GarciaBrian V Geisbrecht
Sep 12, 2012·Immunobiology·Susan M Lea, Steven Johnson
Jun 16, 2015·Frontiers in Immunology·Nicolas S MerleLubka T Roumenina
Sep 9, 2016·Journal of Labelled Compounds & Radiopharmaceuticals·William HsiehChris Tsopelas
Feb 8, 2018·The Journal of Biological Chemistry·Nienke W M de JongSuzan H M Rooijakkers
Mar 17, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brandon L GarciaBrian V Geisbrecht
Nov 9, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jordan L WoehlBrian V Geisbrecht
Dec 1, 2014·Biophysics Reviews·Marni Williams, Richard Baxter
Sep 4, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brandon L GarciaBrian V Geisbrecht
Jul 18, 2017·Frontiers in Cellular and Infection Microbiology·Fermin E GuerraJovanka M Voyich
Jan 10, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xin XuBrian V Geisbrecht
Mar 31, 2019·Microbiology Spectrum·Nienke W M de JongJos A G van Strijp
Aug 28, 2021·International Journal of Molecular Sciences·Francesco Tavanti, Maria Cristina Menziani

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