SOLUTION STRUCTURE OF A FUNCTIONALLY ACTIVE COMPONENT OF DECAY ACCELERATING FACTORSOLUTION STRUCTURE OF A FUNCTIONALLY ACTIVE COMPONENT OF DECAY ACCELERATING FACTOR

Structural highlights

1nwv is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR, 42 models
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DAF_HUMAN This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and c3 activation. Interaction of daf with cell-associated C4b and C3b polypeptides interferes with their ability to catalyze the conversion of C2 and factor B to enzymatically active C2a and Bb and thereby prevents the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade.[1]

Evolutionary Conservation

 

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Ward T, Pipkin PA, Clarkson NA, Stone DM, Minor PD, Almond JW. Decay-accelerating factor CD55 is identified as the receptor for echovirus 7 using CELICS, a rapid immuno-focal cloning method. EMBO J. 1994 Nov 1;13(21):5070-4. PMID:7525274
  2. 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
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