Cellular and Molecular Life Sciences CMLS

, Volume 62, Issue 23, pp 2771–2791 | Cite as

Structural analysis of leucine-rich-repeat variants in proteins associated with human diseases

  • N. Matsushima
  • N. Tachi
  • Y. Kuroki
  • P. Enkhbayar
  • M. Osaki
  • M. Kamiya
  • R. H. Kretsinger
Review

Abstract.

A number of human diseases have been shown to be associated with mutation in the genes encoding leucine-rich-repeat (LRR)-containing proteins. They include 16 different LRR proteins. Mutations of these proteins are associated with 19 human diseases. The mutations occur frequently within the LRR domains as well as their neighboring domains, including cysteine clusters. Here, based on the sequence analysis of the LRR domains and the known structure of LRR proteins, we describe some features of different sequence variants and discuss their adverse effects. The mutations in the cysteine clusters, which preclude the formation of sulfide bridges or lead to a wrong paring of cysteines in extracellular proteins or extracellular domains, occur with high frequency. In contrast, missense mutations at some specific positions in LRRs are very rare or are not observed at all.

Key words.

Leucine-rich repeats human diseases cysteine clusters typical LRR motif RI-like LRR motif Cryopyrin/Nalp3/PYPAF1 CARD15 

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Copyright information

© Birkhäuser Verlag, Basel 2005

Authors and Affiliations

  • N. Matsushima
    • 1
  • N. Tachi
    • 2
  • Y. Kuroki
    • 3
  • P. Enkhbayar
    • 1
    • 4
    • 5
  • M. Osaki
    • 5
  • M. Kamiya
    • 6
  • R. H. Kretsinger
    • 7
  1. 1.Division of Biophysics, School of Health SciencesSapporo Medical UniversityHokkaidoJapan
  2. 2.Department of Occupational Therapy, School of Health SciencesSapporo Medical UniversityHokkaidoJapan
  3. 3.Department of Biochemistry, School of MedicineSapporo Medical UniversityHokkaidoJapan
  4. 4.Department of Biophysics, Faculty of BiologyNational University of MongoliaUlaanbaatarMongolia
  5. 5.Division of Agricultural Science, Graduate School of AgricultureHokkaido UniversityHokkaidoJapan
  6. 6.Division of Biological Science, Graduate School of ScienceHokkaido UniversityHokkaidoJapan
  7. 7.Department of BiologyUniversity of VirginiaCharlottesvilleUSA

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