Clustering of disease-causing mutations on the domain-domain interfaces of ABCC6

Krisztina Fülöp, László Barna, Orsolya Symmons, P. Závodszky, A. Váradi

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Mutations in ABCC6 are responsible for pseudoxanthoma elasticum (PXE), a rare genetic disease affecting the elastic tissues of the body. ABCC6 encodes a 1503 amino acid long ABC transporter, ABCC6/MRP6. The functional link between the impaired activity of the protein and the disease is not known. We have built a homology model of this transporter, and analyzed the distribution of the known 119 missense PXE-associated mutations within the predicted structure. Significant clustering of the missense mutations has been found at complex domain-domain interfaces: at the transmission interface that involves four intracellular loops and the two ABC domains as well as at the ABC-ABC interacting surfaces. The mutations affecting these regions are 2.75 and 3.53-fold more frequent than the average mutational rate along the transporter protein sequence. These data provide a genetic proof of the importance of these domain-domain interactions in the ABCC6 transporter.

Original languageEnglish
Pages (from-to)706-709
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume379
Issue number3
DOIs
Publication statusPublished - Feb 13 2009

Fingerprint

Rubber
Pseudoxanthoma Elasticum
Cluster Analysis
Mutation
ATP-Binding Cassette Transporters
Inborn Genetic Diseases
Proteins
Elastic Tissue
Missense Mutation
Tissue
Rare Diseases
Amino Acids

Keywords

  • ABC transporters
  • Genetic disease
  • Homology model
  • Missense mutations
  • Pseudoxanthoma elasticum

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Clustering of disease-causing mutations on the domain-domain interfaces of ABCC6. / Fülöp, Krisztina; Barna, László; Symmons, Orsolya; Závodszky, P.; Váradi, A.

In: Biochemical and Biophysical Research Communications, Vol. 379, No. 3, 13.02.2009, p. 706-709.

Research output: Contribution to journalArticle

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