3t48

From Proteopedia

Crystal Structure of truncated form of Staphylococcal Complement Inhibitor D (SCIN-D) at 1.5 Angstrom

Structural highlights

3t48 is a 2 chain structure with sequence from Staphylococcus aureus subsp. aureus Mu50. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.5Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A0H3JPM4_STAAM Involved in countering the first line of host defense mechanisms. Efficiently inhibits opsonization, phagocytosis and killing of S.aureus by human neutrophils. Acts by binding and stabilizing human C3 convertases (C4b2a and C3bBb), leading to their inactivation. The convertases are no longer able to cleave complement C3, therefore preventing further C3b deposition on the bacterial surface and phagocytosis of the bacterium. Also prevents C5a-induced neutrophil responses.[ARBA:ARBA00025334]

Publication Abstract from PubMed

To survive in immune-competent hosts, the pathogen Staphylococcus aureus expresses and secretes a sophisticated array of proteins that inhibit the complement system. Among these are the staphylococcal complement inhibitors (SCIN), which are composed of three active proteins (SCIN-A, -B, and -C) and one purportedly inactive member (SCIN-D or ORF-D). Because previous work has focused almost exclusively on SCIN-A, we sought to provide initial structure/function information on additional SCIN proteins. To this end we determined crystal structures of an active, N-terminal truncation mutant of SCIN-B (denoted SCIN-B(18-85)) both free and bound to the C3c fragment of complement component C3 at 1.5 and 3.4 A resolution, respectively. Comparison of the C3c/SCIN-B(18-85) structure with that of C3c/SCIN-A revealed that both proteins target the same functional hotspot on the C3b/C3c surface yet harbor diversity in both the type of residues and interactions formed at their C3b/C3c interfaces. Most importantly, these structures allowed identification of Arg(44) and Tyr(51) as residues key for SCIN-B binding to C3b and subsequent inhibition of the AP C3 convertase. In addition, we also solved several crystal structures of SCIN-D to 1.3 A limiting resolution. This revealed an unexpected structural deviation in the N-terminal alpha helix relative to SCIN-A and SCIN-B. Comparative analysis of both electrostatic potentials and surface complementarity suggest a physical explanation for the inability of SCIN-D to bind C3b/C3c. Together, these studies provide a more thorough understanding of immune evasion by S. aureus and enhance potential use of SCIN proteins as templates for design of complement targeted therapeutics.

Diversity in the C3b Convertase Contact Residues and Tertiary Structures of the Staphylococcal Complement Inhibitor (SCIN) Protein Family.,Garcia BL, Summers BJ, Lin Z, Ramyar KX, Ricklin D, Kamath DV, Fu ZQ, Lambris JD, Geisbrecht BV J Biol Chem. 2012 Jan 2;287(1):628-40. Epub 2011 Nov 15. PMID:22086928^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Garcia BL, Summers BJ, Lin Z, Ramyar KX, Ricklin D, Kamath DV, Fu ZQ, Lambris JD, Geisbrecht BV. Diversity in the C3b Convertase Contact Residues and Tertiary Structures of the Staphylococcal Complement Inhibitor (SCIN) Protein Family. J Biol Chem. 2012 Jan 2;287(1):628-40. Epub 2011 Nov 15. PMID:22086928 doi:10.1074/jbc.M111.298984