Pinpointing the putative heparin/sialic acid-binding residues in the 'sushi' domain 7 of factor H: a molecular modeling study.

S. Ranganathan, D. A. Male, R. J. Ormsby, E. Giannakis, D. L. Gordon

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Factor H, a secretory glycoprotein comprising 20 short consensus repeat (SCR) or 'sushi' domains of about 60 amino acids each, is a regulator of the complement system. The complement-regulatory functions of factor H are targeted by its binding to polyanions such as heparin/sialic acid, involving SCRs 7 and 20. Recently, the SCR 7 heparin-binding site was shown to be co-localized with the Streptococcus Group A M protein binding site on factor H (T.K. Blackmore et al., Infect. Immun. 66, 1427 (1998)). Using sequence analysis of all heparin-binding domains of factor H and its closest homologues, molecular modeling of SCRs 6 and 7, and surface electrostatic potential studies, the residues implicated in heparin/sialic acid binding to SCR 7 have been localized to four regions of sequence space containing stretches of basic as well as histidine residues. The heparin-binding site is spatially compact and lies near the interface between SCRs 6 and 7, with residues in the interdomain linker playing a significant role.

LanguageEnglish
Pages155-167
Number of pages13
JournalPacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
Publication statusPublished - 2000
Externally publishedYes

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Complement Factor H
N-Acetylneuraminic Acid
Heparin
Binding Sites
Streptococcus pyogenes
Static Electricity
Histidine
Protein Binding
Sequence Analysis
Glycoproteins
Amino Acids

Cite this

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title = "Pinpointing the putative heparin/sialic acid-binding residues in the 'sushi' domain 7 of factor H: a molecular modeling study.",
abstract = "Factor H, a secretory glycoprotein comprising 20 short consensus repeat (SCR) or 'sushi' domains of about 60 amino acids each, is a regulator of the complement system. The complement-regulatory functions of factor H are targeted by its binding to polyanions such as heparin/sialic acid, involving SCRs 7 and 20. Recently, the SCR 7 heparin-binding site was shown to be co-localized with the Streptococcus Group A M protein binding site on factor H (T.K. Blackmore et al., Infect. Immun. 66, 1427 (1998)). Using sequence analysis of all heparin-binding domains of factor H and its closest homologues, molecular modeling of SCRs 6 and 7, and surface electrostatic potential studies, the residues implicated in heparin/sialic acid binding to SCR 7 have been localized to four regions of sequence space containing stretches of basic as well as histidine residues. The heparin-binding site is spatially compact and lies near the interface between SCRs 6 and 7, with residues in the interdomain linker playing a significant role.",
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year = "2000",
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journal = "Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing",

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Pinpointing the putative heparin/sialic acid-binding residues in the 'sushi' domain 7 of factor H : a molecular modeling study. / Ranganathan, S.; Male, D. A.; Ormsby, R. J.; Giannakis, E.; Gordon, D. L.

In: Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing, 2000, p. 155-167.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Pinpointing the putative heparin/sialic acid-binding residues in the 'sushi' domain 7 of factor H

T2 - Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing

AU - Ranganathan, S.

AU - Male, D. A.

AU - Ormsby, R. J.

AU - Giannakis, E.

AU - Gordon, D. L.

PY - 2000

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AB - Factor H, a secretory glycoprotein comprising 20 short consensus repeat (SCR) or 'sushi' domains of about 60 amino acids each, is a regulator of the complement system. The complement-regulatory functions of factor H are targeted by its binding to polyanions such as heparin/sialic acid, involving SCRs 7 and 20. Recently, the SCR 7 heparin-binding site was shown to be co-localized with the Streptococcus Group A M protein binding site on factor H (T.K. Blackmore et al., Infect. Immun. 66, 1427 (1998)). Using sequence analysis of all heparin-binding domains of factor H and its closest homologues, molecular modeling of SCRs 6 and 7, and surface electrostatic potential studies, the residues implicated in heparin/sialic acid binding to SCR 7 have been localized to four regions of sequence space containing stretches of basic as well as histidine residues. The heparin-binding site is spatially compact and lies near the interface between SCRs 6 and 7, with residues in the interdomain linker playing a significant role.

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