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Complement regulation at the molecular level: The structure of decay-accelerating factor

Complement regulation at the molecular level: The structure of decay-accelerating factor
Complement regulation at the molecular level: The structure of decay-accelerating factor

The human complement regulator CD55 is a key molecule protecting self-cells from complement-mediated lysis. X-ray diffraction and analytical ultracentrifugation data reveal a rod-like arrangement of four short consensus repeat (SCR) domains in both the crystal and solution. The stalk linking the four SCR domains to the glycosylphosphatidylinositol anchor is extended by the addition of 11 highly charged O-glycans and positions the domains an estimated 177 Å above the membrane. Mutation mapping and hydrophobic potential analysis suggest that the interaction with the convertase, and thus complement regulation, depends on the burial of a hydrophobic patch centered on the linker between SCR domains 2 and 3.

CD55, Complement regulator, Glycoprotein, Pathogen receptor
0027-8424
1279-1284
Lukacik, P.
3024b3ea-3de0-4820-a0cc-5081c062a9c4
Roversi, P.
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White, J.
d3286671-ff76-48aa-aac4-6317fed0e989
Esser, D.
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Smith, G.P.
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Billington, J.
efe4a5bb-852b-4ae6-a66a-b34deda06643
Williams, P.A.
18f55b81-ad5c-4db1-892a-9bdcc5092a6b
Rudd, P.M.
61889150-348c-4c38-b0ca-25f84641584f
Wormald, M.R.
f717e6d1-4378-4417-8ab2-0f78e9176044
Harvey, D.J.
a8e787b1-801c-4e66-b5a1-6265570b519d
Crispin, M.
cd980957-0943-4b89-b2b2-710f01f33bc9
Radcliffe, C.M.
56cdc472-e151-4a5f-875c-3254befe9d46
Dwek, R.A.
06a873cf-f7f5-467f-99f3-d168b896da27
Evans, D.J.
331a6db3-9b2e-4659-80ce-ae8ae7ddc1b5
Morgan, B.P.
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Smith, R.A.G.
cc0a11f6-bb25-4c0d-877b-15e38cbe2fc9
Lea, S.M.
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Lukacik, P.
3024b3ea-3de0-4820-a0cc-5081c062a9c4
Roversi, P.
5645a826-2059-4add-b0f4-c1f761fe2e11
White, J.
d3286671-ff76-48aa-aac4-6317fed0e989
Esser, D.
7f07f05b-1882-45c7-a048-422dbcd1b2d7
Smith, G.P.
60ac8fb2-5711-4ac1-ab02-274f074300f7
Billington, J.
efe4a5bb-852b-4ae6-a66a-b34deda06643
Williams, P.A.
18f55b81-ad5c-4db1-892a-9bdcc5092a6b
Rudd, P.M.
61889150-348c-4c38-b0ca-25f84641584f
Wormald, M.R.
f717e6d1-4378-4417-8ab2-0f78e9176044
Harvey, D.J.
a8e787b1-801c-4e66-b5a1-6265570b519d
Crispin, M.
cd980957-0943-4b89-b2b2-710f01f33bc9
Radcliffe, C.M.
56cdc472-e151-4a5f-875c-3254befe9d46
Dwek, R.A.
06a873cf-f7f5-467f-99f3-d168b896da27
Evans, D.J.
331a6db3-9b2e-4659-80ce-ae8ae7ddc1b5
Morgan, B.P.
56398ab3-c1e1-4757-8b12-c5c223257055
Smith, R.A.G.
cc0a11f6-bb25-4c0d-877b-15e38cbe2fc9
Lea, S.M.
98eb37ac-ed66-4022-93ee-2ac8a73e824a

Lukacik, P., Roversi, P., White, J., Esser, D., Smith, G.P., Billington, J., Williams, P.A., Rudd, P.M., Wormald, M.R., Harvey, D.J., Crispin, M., Radcliffe, C.M., Dwek, R.A., Evans, D.J., Morgan, B.P., Smith, R.A.G. and Lea, S.M. (2004) Complement regulation at the molecular level: The structure of decay-accelerating factor. Proceedings of the National Academy of Sciences, 101 (5), 1279-1284. (doi:10.1073/pnas.0307200101).

Record type: Article

Abstract

The human complement regulator CD55 is a key molecule protecting self-cells from complement-mediated lysis. X-ray diffraction and analytical ultracentrifugation data reveal a rod-like arrangement of four short consensus repeat (SCR) domains in both the crystal and solution. The stalk linking the four SCR domains to the glycosylphosphatidylinositol anchor is extended by the addition of 11 highly charged O-glycans and positions the domains an estimated 177 Å above the membrane. Mutation mapping and hydrophobic potential analysis suggest that the interaction with the convertase, and thus complement regulation, depends on the burial of a hydrophobic patch centered on the linker between SCR domains 2 and 3.

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More information

Published date: 3 February 2004
Keywords: CD55, Complement regulator, Glycoprotein, Pathogen receptor

Identifiers

Local EPrints ID: 414575
URI: http://eprints.soton.ac.uk/id/eprint/414575
ISSN: 0027-8424
PURE UUID: 84d528bd-0f48-48d4-b696-1c29b551f250
ORCID for M. Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 04 Oct 2017 16:30
Last modified: 17 Dec 2019 01:27

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Contributors

Author: P. Lukacik
Author: P. Roversi
Author: J. White
Author: D. Esser
Author: G.P. Smith
Author: J. Billington
Author: P.A. Williams
Author: P.M. Rudd
Author: M.R. Wormald
Author: D.J. Harvey
Author: M. Crispin ORCID iD
Author: C.M. Radcliffe
Author: R.A. Dwek
Author: D.J. Evans
Author: B.P. Morgan
Author: R.A.G. Smith
Author: S.M. Lea

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