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3L5N

Staphylococcal Complement Inhibitor (SCIN) in complex with Human Complement Component C3b

Summary for 3L5N
Entry DOI10.2210/pdb3l5n/pdb
Related3L3O
DescriptorComplement C3, Staphylococcal complement inhibitor, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
Functional Keywordscomplement alternate pathway, complement pathway, converstase, immune response, inflammatory response, innate immunity, secreted, virulence, immune evasion, immune system
Biological sourceStaphylococcus aureus
More
Cellular locationSecreted: P01024 P01024 Q931M7
Total number of polymer chains3
Total formula weight186374.63
Authors
Geisbrecht, B.V.,Garcia, B.L. (deposition date: 2009-12-22, release date: 2010-08-04, Last modification date: 2024-10-16)
Primary citationGarcia, B.L.,Ramyar, K.X.,Tzekou, A.,Ricklin, D.,McWhorter, W.J.,Lambris, J.D.,Geisbrecht, B.V.
Molecular Basis for Complement Recognition and Inhibition Determined by Crystallographic Studies of the Staphylococcal Complement Inhibitor (SCIN) Bound to C3c and C3b.
J.Mol.Biol., 402:17-29, 2010
Cited by
PubMed 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 H and factor B. Our results give insight into SCIN binding to activated derivatives of C3, explain how SCIN can recognize C3b in the absence of other complement components, and provide a structural basis for the competitive C3b-binding properties of SCIN. In the future, this may suggest templates for the design of novel complement inhibitors based upon the SCIN structure.
PubMed: 20654625
DOI: 10.1016/j.jmb.2010.07.029
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (7.536 Å)
Structure validation

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数据于2024-11-06公开中

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