umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Disease-causing mutations in the cellular retinaldehyde binding protein tighten and abolish ligand interactions
Umeå University, Faculty of Medicine, Department of Medical Biosciences.
Show others and affiliations
2003 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 278, no 14, 12397-12402 p.Article in journal (Refereed) Published
Abstract [en]

Mutations in the human cellular retinaldehyde binding protein (CRALBP) gene cause retinal pathology. To understand the molecular basis of impaired CRALBP function, we have characterized human recombinant CRALBP containing the disease causing mutations R233W or M225K. Protein structures were verified by amino acid analysis and mass spectrometry, retinoid binding properties were evaluated by UV-visible and fluorescence spectroscopy and substrate carrier functions were assayed for recombinant 11-cis-retinol dehydrogenase (rRDH5). The M225K mutant was less soluble than the R233W mutant and lacked retinoid binding capability and substrate carrier function. In contrast, the R233W mutant exhibited solubility comparable to wild type rCRALBP and bound stoichiometric amounts of 11-cis- and 9-cis-retinal with at least 2-fold higher affinity than wild type rCRALBP. Holo-R233W significantly decreased the apparent affinity of rRDH5 for 11-cis-retinoid relative to wild type rCRALBP. Analyses by heteronuclear single quantum correlation NMR demonstrated that the R233W protein exhibits a different conformation than wild type rCRALBP, including a different retinoid-binding pocket conformation. The R233W mutant also undergoes less extensive structural changes upon photoisomerization of bound ligand, suggesting a more constrained structure than that of the wild type protein. Overall, the results show that the M225K mutation abolishes and the R233W mutation tightens retinoid binding and both impair CRALBP function in the visual cycle as an 11-cis-retinol acceptor and as a substrate carrier.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2003. Vol. 278, no 14, 12397-12402 p.
Keyword [en]
Disease-causing mutations
National Category
Ophthalmology
Research subject
Ophtalmology; Genetics
Identifiers
URN: urn:nbn:se:umu:diva-35426DOI: 10.1074/jbc.M207300200PubMedID: 12536144Local ID: 744OAI: oai:DiVA.org:umu-35426DiVA: diva2:344182
Available from: 2010-08-18 Created: 2010-08-18 Last updated: 2017-12-12Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Golovleva, IrinaBurstedt, MarieSandgren, Ola

Search in DiVA

By author/editor
Golovleva, IrinaBurstedt, MarieForsman, KristinaHolmgren, GöstaSandgren, Ola
By organisation
Department of Medical BiosciencesOphthalmology
In the same journal
Journal of Biological Chemistry
Ophthalmology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 129 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf