1nwv
SOLUTION STRUCTURE OF A FUNCTIONALLY ACTIVE COMPONENT OF DECAY ACCELERATING FACTOR
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OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Blood group Cromer OMIM:[125240], Blood group, Knops system OMIM:[120620], CR1 deficiency OMIM:[120620], Malaria, severe, resistance to OMIM:[120620], SLE susceptibility OMIM:[120620]
About this StructureAbout this Structure
1NWV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
Page seeded by OCA on Mon Nov 12 18:26:45 2007