The factor H variant associated with age-related macular degeneration (H384) and the non-disease associated form bind differentially to C-reactive protein, fibromodulin, DNA and necrotic cells.

Holmér, Andreas (author): Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Proteinkemi, Malmö,Clinical Chemistry, Malmö,Lund University Research Groups,Protein Chemistry, Malmö

Trouw, Leendert (author): Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Proteinkemi, Malmö,Clinical Chemistry, Malmö,Lund University Research Groups,Protein Chemistry, Malmö

Clark, Simon J (author)

Sjolander, Jonatan (author)

Heinegård, Dick (author): Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine

Sim, Robert B (author)

Day, Anthony J (author)

Blom, Anna (author): Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups

(creator_code:org_t)

2007
2007
English.
In: Journal of Biological Chemistry. - 1083-351X. ; 282:15, s. 10894-10900

Related links:: http://www.ncbi.nlm.... (free); show more...; http://dx.doi.org/10... (free); https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Abstract Subject headings

Recently, a polymorphism in the complement regulator factor H (FH) gene has been associated with age-related macular degeneration. When histidine instead of tyrosine is present at position 384 in the seventh complement control protein (CCP) domain of FH, the risk for age-related macular degeneration is increased. It was recently shown that these allotypic variants of FH, in the context of a recombinant construct corresponding to CCPs 6 - 8, recognize polyanionic structures differently, which may lead to altered regulation of the alternative pathway of complement. We show now that His-384, corresponding to the risk allele, binds C-reactive protein (CRP) poorly compared with the Tyr-384 form. We also found that C1q and phosphorylcholine do not compete with FH for binding to C-reactive protein. The interaction with extracellular matrix protein fibromodulin, which we now show to be mediated, at least in part, by CCP6 - 8 of FH, occurs via the polypeptide of fibromodulin and not through its glycosaminoglycan modifications. The Tyr-384 variant of FH bound fibromodulin better than the His-384 form. Furthermore, we find that CCP6 - 8 is able to interact with DNA and necrotic cells, but in contrast the His-384 allotype binds these ligands more strongly than the Tyr-384 variant. The variations in binding affinity of the two alleles indicate that complement activation and local inflammation in response to different targets will differ between His/His and Tyr/Tyr homozygotes.

By the author/editor: Holmér, Andreas; Trouw, Leendert; Clark, Simon J; Sjolander, Jonat ...; Heinegård, Dick; Sim, Robert B; show more...; Day, Anthony J; Blom, Anna; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Other Basic Medi ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medicinal Chemis ...

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