The second and third modules of human decay accelerating factor (DAF) are necessary and sufficient to accelerate decay of the classical pathway (CP) convertase of complement. No structure of a mammalian protein with decay-accelerating activity has been available to date. We therefore determined the solution structure of DAF modules 2 and 3 (DAF approximately 2,3). Structure-guided analysis of 24 mutants identified likely contact points between DAF and the CP convertase. Three (R96, R69, and a residue in the vicinity of L171) lie on DAF approximately 2,3's concave face. A fourth, consisting of K127 and nearby R100, is on the opposite face. Regions of module 3 remote from the semiflexible 2-3 interface seem not to be involved in binding to the CP convertase. DAF thus seems to occupy a groove on the CP convertase such that both faces of DAF close to the 2-3 junction (including a positively charged region that encircles the protein at this point) interact simultaneously. Alternative pathway convertase interactions with DAF require additional regions of CCP 3 lying away from the 2-3 interface, consistent with the established additional requirement of module 4 for alternative pathway regulation.
Solution structure of a functionally active fragment of decay-accelerating factor.,Uhrinova S, Lin F, Ball G, Bromek K, Uhrin D, Medof ME, Barlow PN Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4718-23. Epub 2003 Apr 2. PMID:12672958
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↑ Uhrinova S, Lin F, Ball G, Bromek K, Uhrin D, Medof ME, Barlow PN. Solution structure of a functionally active fragment of decay-accelerating factor. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4718-23. Epub 2003 Apr 2. PMID:12672958 doi:10.1073/pnas.0730844100