2WIN

C3 convertase (C3bBb) stabilized by SCIN

Summary for 2WIN

• Entry DOI: 10.2210/pdb2win/pdb
• Related: 1DLE 1Q0P 1RRK 1RTK 2A73 2A74 2I6Q 2ICF 2QFF 2WII
• Descriptor: COMPLEMENT C3 BETA CHAIN, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (17 entities in total)
• Functional Keywords: serine protease, immune response, innate immunity, zymogen, secreted, protease, glycation, alternative pathway, disease mutation, hydrolase, convertase, complement, polymorphism, immune evasion, immune system
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted: P01024 P01024 Q6GFB4
• Total number of polymer chains: 16
• Total formula weight: 984828.88

Authors

Wu, J.,Janssen, B.J.,Gros, P. (deposition date: 2009-05-13, release date: 2009-06-09, Last modification date: 2023-12-13)

Primary citation

Rooijakkers, S.H.,Wu, J.,Ruyken, M.,van Domselaar, R.,Planken, K.L.,Tzekou, A.,Ricklin, D.,Lambris, J.D.,Janssen, B.J.,van Strijp, J.A.,Gros, P.
Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor.
Nat. Immunol., 10:721-727, 2009

PubMed Abstract: Activation of the complement system generates potent chemoattractants and leads to the opsonization of cells for immune clearance. Short-lived protease complexes cleave complement component C3 into anaphylatoxin C3a and opsonin C3b. Here we report the crystal structure of the C3 convertase formed by C3b and the protease fragment Bb, which was stabilized by the bacterial immune-evasion protein SCIN. The data suggest that the proteolytic specificity and activity depend on the formation of dimers of C3 with C3b of the convertase. SCIN blocked the formation of a productive enzyme-substrate complex. Irreversible dissociation of the complex of C3b and Bb is crucial to complement regulation and was determined by slow binding kinetics of the Mg(2+)-adhesion site in Bb. Understanding the mechanistic basis of the central complement-activation step and microbial immune evasion strategies targeting this step will aid in the development of complement therapeutics.

PubMed: 19503103
DOI: 10.1038/ni.1756

Experimental method

X-RAY DIFFRACTION (3.9 Å)