Journal of Molecular Modeling

, Volume 15, Issue 2, pp 113–122

An interrupted beta-propeller and protein disorder: structural bioinformatics insights into the N-terminus of alsin

  • Dinesh C. Soares
  • Paul N. Barlow
  • David J. Porteous
  • Rebecca S. Devon
Original Paper

DOI: 10.1007/s00894-008-0381-1

Cite this article as:
Soares, D.C., Barlow, P.N., Porteous, D.J. et al. J Mol Model (2009) 15: 113. doi:10.1007/s00894-008-0381-1

Abstract

Defects in the human ALS2 gene, which encodes the 1,657-amino-acid residue protein alsin, are linked to several related motor neuron diseases. We created a structural model for the N-terminal 690-residue region of alsin through comparative modelling based on regulator of chromosome condensation 1 (RCC1). We propose that this alsin region contains seven RCC1-like repeats in a seven-bladed beta-propeller structure. The propeller is formed by a double clasp arrangement containing two segments (residues 1–218 and residues 525–690). The 306-residue insert region, predicted to lie within blade 5 and to be largely disordered, is poorly conserved across species. Surface patches of evolutionary conservation probably indicate locations of binding sites. Both disease-causing missense mutations—Cys157Tyr and Gly540Glu—are buried in the propeller and likely to be structurally disruptive. This study aids design of experimental studies by highlighting the importance of construct length, will enhance interpretation of protein–protein interactions, and enable rational site-directed mutagenesis.

Keywords

AlsinBeta-propellerComparative modelingFold recognitionProtein disorderRCC1-repeat

Supplementary material

894_2008_381_MOESM1_ESM.pdf (906 kb)
ESM 1(PDF 906 KB).

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Dinesh C. Soares
    • 1
    • 2
  • Paul N. Barlow
    • 2
    • 3
  • David J. Porteous
    • 1
  • Rebecca S. Devon
    • 1
  1. 1.Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General HospitalUniversity of EdinburghEdinburghUK
  2. 2.School of ChemistryUniversity of EdinburghEdinburghUK
  3. 3.Institute of Structural and Molecular BiologyUniversity of EdinburghEdinburghUK