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The factor H varian...
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Holmér, AndreasLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Proteinkemi, Malmö,Clinical Chemistry, Malmö,Lund University Research Groups,Protein Chemistry, Malmö
(författare)
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.
- Artikel/kapitelEngelska2007
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LIBRIS-ID:oai:lup.lub.lu.se:f6b3225e-a46b-4c04-91ca-353518f7feb2
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https://lup.lub.lu.se/record/165759URI
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https://doi.org/10.1074/jbc.M610256200DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
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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.
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Trouw, LeendertLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Proteinkemi, Malmö,Clinical Chemistry, Malmö,Lund University Research Groups,Protein Chemistry, Malmö(Swepub:lu)klke-ltr
(författare)
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Clark, Simon J
(författare)
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Sjolander, Jonatan
(författare)
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Heinegård, DickLund 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(Swepub:lu)medk-dhe
(författare)
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Sim, Robert B
(författare)
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Day, Anthony J
(författare)
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Blom, AnnaLund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups(Swepub:lu)klke-abl
(författare)
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Klinisk kemi, MalmöForskargrupper vid Lunds universitet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Biological Chemistry282:15, s. 10894-109001083-351X
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