1RS0

Crystal Structure Analysis of the Bb segment of Factor B complexed with Di-isopropyl-phosphate (DIP)

Summary for 1RS0

• Entry DOI: 10.2210/pdb1rs0/pdb
• Related: 1RRK 1RTK
• Descriptor: Complement factor B, IODIDE ION, SODIUM ION, ... (6 entities in total)
• Functional Keywords: factor b, bb, factor bb-dip complex, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P00751
• Total number of polymer chains: 1
• Total formula weight: 56851.36

Authors

Ponnuraj, K.,Xu, Y.,Macon, K.,Moore, D.,Volanakis, J.E.,Narayana, S.V. (deposition date: 2003-12-09, release date: 2004-12-14, Last modification date: 2024-10-09)

Primary citation

Ponnuraj, K.,Xu, Y.,Macon, K.,Moore, D.,Volanakis, J.E.,Narayana, S.V.
Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase.
Mol.Cell, 14:17-28, 2004

PubMed Abstract: The C-terminal fragment, Bb, of factor B combines with C3b to form the pivotal C3-convertase, C3bBb, of alternative complement pathway. Bb consists of a von Willebrand factor type A (vWFA) domain that is structurally similar to the I domains of integrins and a serine protease (SP) domain that is in inactive conformation. The structure of the C3bBb complex would be important in deciphering the activation mechanism of the SP domain. However, C3bBb is labile and not amenable to X-ray diffraction studies. We engineered a disulfide bond in the vWFA domain of Bb homologous to that shown to lock I domains in active conformation. The crystal structures of Bb(C428-C435) and its inhibitor complexes reveal that the adoption of the "active" conformation by the vWFA domain is not sufficient to activate the C3-convertase catalytic apparatus and also provide insights into the possible mode of C3-convertase activation.

PubMed: 15068800
DOI: 10.1016/S1097-2765(04)00160-1

Experimental method

X-RAY DIFFRACTION (2.6 Å)