cd55.htm

Decay Accelerating Factor
Pietro Roversi and Rachel Abbott with Prof. B.P. Morgan (University of Wales College of Medicine) and Dr. R.B. Sim (MRC Immunochemistry Unit, Oxford)

Lea Group

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Structures

Decay Accelerating Factor (DAF, CD55) is a membrane associated regulator of complement activation that contains four ~60 amino acid long consensus sequences termed complement control protein repeats (CCPs) or short consensus repeats (SCRs). The four SCRs comprise the functional portion of the protein and are linked to the plasma membrane via a heavily glycosylated serine/threonine rich linker and a glycophophyditdylinositol (GPI) anchor. CD55 is a multi-functional molecule accelerating the decay of both the classical and alternative pathway C3 convertases, binding CD97 a member of the EGF-TM7 family whose expression is rapidly upregulated on T and B cells following activation, and acting as the receptor for a variety of viral and bacterial pathogens. Domain swapping studies for a variety of CD55 interactions have shown that multiple domains are essential for biological function and the precise arrangement of any one SCR domain with respect to the others is therefore crucial to a full understanding of the biology.
Using data collected from ESRF and Daresbury we have solved the structure (at 1.7A) of the lower two SCR domains of CD55 in several crystal forms using MIRAS and have also solved the structure of a construct consisting of all four extracellular SCR domains. These structures suggest that the SCR domains associate in a relatively rigid manner to produce a highly extended architecture. We are now trying to use these structures to better understand the various biologies associated with this molecule.

Biological activity, membrane-targeting modification and crystallisation of soluble human decay accelerating factor expressed in E.coli.

White et al. , Protein Science, 13, 2406-2415

From structure to function of a complement regulator: Decay accelerating factor (CD55)
Lukacik et al. , in Structural Biology of the Complement System, ed Lambris In the press

Complement regulation at the molecular level: the structure of Decay Accelerating Factor.
Lukacik et al., Proc. Natl. Acad. Sci. USA, 105(5), 1279-1284 (2004). [PDB IDs: 1ojv , 1ojw , 1ojy , 1ok2 , 1ok3 , 1ok1 , 1ok9 ]

Mapping CD55 function. The structure of two pathogen-binding domains at 1.7 A.
Williams et al., J Biol Chem. 2003 Mar 21;278(12):10691-6. [PDB IDs: 1h04 , 1h03 , 1h2p , 1h2q , 1uot ]

Interactions of CD55 with non-complement ligands.
Lea, S., Biochem Soc Trans. 2002 Nov;30(Pt 6):1014-9.

Crystallization and preliminary X-ray diffraction analysis of a biologically active fragment of CD55.
Lea et al., Acta Crystallogr D Biol Crystallogr. 1999 Jun;55 ( Pt 6):1198-200.