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

P Lukacik; P Roversi; J White; D Esser; GP Smith; J Billington; PA Williams; PM Rudd; MR Wormald; DJ Harvey; MDM Crispin; CM Radcliffe; RA Dwek; DJ Evans; BP Morgan; RAG Smith; SM Lea

doi:10.1073/pnas.0307200101

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

P Lukacik, P Roversi, J White, D Esser, GP Smith, J Billington, PA Williams, PM Rudd, MR Wormald, DJ Harvey, MDM Crispin, CM Radcliffe, RA Dwek, DJ Evans, BP Morgan, RAG Smith, SM Lea^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

109 Citations (Scopus)

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 Angstrom 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.

Original language	English
Pages (from-to)	1279-1284
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	101
Issue number	5
DOIs	https://doi.org/10.1073/pnas.0307200101
Publication status	Published - 3 Feb 2004

Keywords

CD55
complement regulator
pathogen receptor
glycoprotein
OVINE SUBMAXILLARY MUCIN
O-LINKED GLYCOPROTEINS
GLYCOSYLATION SITES
CONTROL PROTEIN
RECEPTOR CD97
C3 CONVERTASE
LIGAND CD55
A DOMAIN
FACTOR-H
BINDING

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Lukacik, P., Roversi, P., White, J., Esser, D., Smith, GP., Billington, J., Williams, PA., Rudd, PM., Wormald, MR., Harvey, DJ., Crispin, MDM., Radcliffe, CM., Dwek, RA., Evans, DJ., Morgan, BP., Smith, RAG., & Lea, SM. (2004). Complement regulation at the molecular level: The structure of decay-accelerating factor. Proceedings of the National Academy of Sciences of the United States of America, 101(5), 1279-1284. https://doi.org/10.1073/pnas.0307200101

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title = "Complement regulation at the molecular level: The structure of decay-accelerating factor",

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 Angstrom 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.",

keywords = "CD55, complement regulator, pathogen receptor, glycoprotein, OVINE SUBMAXILLARY MUCIN, O-LINKED GLYCOPROTEINS, GLYCOSYLATION SITES, CONTROL PROTEIN, RECEPTOR CD97, C3 CONVERTASE, LIGAND CD55, A DOMAIN, FACTOR-H, BINDING",

author = "P Lukacik and P Roversi and J White and D Esser and GP Smith and J Billington and PA Williams and PM Rudd and MR Wormald and DJ Harvey and MDM Crispin and CM Radcliffe and RA Dwek and DJ Evans and BP Morgan and RAG Smith and SM Lea",

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doi = "10.1073/pnas.0307200101",

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Lukacik, P, Roversi, P, White, J, Esser, D, Smith, GP, Billington, J, Williams, PA, Rudd, PM, Wormald, MR, Harvey, DJ, Crispin, MDM, Radcliffe, CM, Dwek, RA, Evans, DJ, Morgan, BP, Smith, RAG & Lea, SM 2004, 'Complement regulation at the molecular level: The structure of decay-accelerating factor', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 5, pp. 1279-1284. https://doi.org/10.1073/pnas.0307200101

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T1 - Complement regulation at the molecular level: The structure of decay-accelerating factor

AU - Lukacik, P

AU - Roversi, P

AU - White, J

AU - Esser, D

AU - Smith, GP

AU - Billington, J

AU - Williams, PA

AU - Rudd, PM

AU - Wormald, MR

AU - Harvey, DJ

AU - Crispin, MDM

AU - Radcliffe, CM

AU - Dwek, RA

AU - Evans, DJ

AU - Morgan, BP

AU - Smith, RAG

AU - Lea, SM

PY - 2004/2/3

Y1 - 2004/2/3

N2 - 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 Angstrom 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.

AB - 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 Angstrom 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.

KW - CD55

KW - complement regulator

KW - pathogen receptor

KW - glycoprotein

KW - OVINE SUBMAXILLARY MUCIN

KW - O-LINKED GLYCOPROTEINS

KW - GLYCOSYLATION SITES

KW - CONTROL PROTEIN

KW - RECEPTOR CD97

KW - C3 CONVERTASE

KW - LIGAND CD55

KW - A DOMAIN

KW - FACTOR-H

KW - BINDING

U2 - 10.1073/pnas.0307200101

DO - 10.1073/pnas.0307200101

M3 - Article

SN - 0027-8424

VL - 101

SP - 1279

EP - 1284

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 5

ER -

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

Abstract

Keywords

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