2XWA

Crystal Structure of Complement Factor D Mutant R202A

Summary for 2XWA

• Entry DOI: 10.2210/pdb2xwa/pdb
• Related: 1BIO 1DFP 1DIC 1DST 1DSU 1FDP 1HFD 2XW9 2XWB 2XWJ
• Descriptor: COMPLEMENT FACTOR D, GLYCEROL (3 entities in total)
• Functional Keywords: immune system, hydrolase, serine protease, alternative pathway
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted: P00746
• Total number of polymer chains: 2
• Total formula weight: 48889.57

Authors

Forneris, F.,Ricklin, D.,Wu, J.,Tzekou, A.,Wallace, R.S.,Lambris, J.D.,Gros, P. (deposition date: 2010-11-01, release date: 2011-01-12, Last modification date: 2024-11-13)

Primary citation

Forneris, F.,Ricklin, D.,Wu, J.,Tzekou, A.,Wallace, R.S.,Lambris, J.D.,Gros, P.
Structures of C3B in Complex with Factors B and D Give Insight Into Complement Convertase Formation.
Science, 330:1816-, 2010

PubMed Abstract: Activation of the complement cascade induces inflammatory responses and marks cells for immune clearance. In the central complement-amplification step, a complex consisting of surface-bound C3b and factor B is cleaved by factor D to generate active convertases on targeted surfaces. We present crystal structures of the pro-convertase C3bB at 4 angstrom resolution and its complex with factor D at 3.5 angstrom resolution. Our data show how factor B binding to C3b forms an open "activation" state of C3bB. Factor D specifically binds the open conformation of factor B through a site distant from the catalytic center and is activated by the substrate, which displaces factor D's self-inhibitory loop. This concerted proteolytic mechanism, which is cofactor-dependent and substrate-induced, restricts complement amplification to C3b-tagged target cells.

PubMed: 21205667
DOI: 10.1126/SCIENCE.1195821

Experimental method

X-RAY DIFFRACTION (2.8 Å)