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An interrupted beta-propeller and protein disorder: structural bioinformatics insights into the N-terminus of alsin
- Source :
- Journal of Molecular Modeling. 15:113-122
- Publication Year :
- 2008
- Publisher :
- Springer Science and Business Media LLC, 2008.
-
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.
- Subjects :
- Models, Molecular
Repetitive Sequences, Amino Acid
Molecular Sequence Data
Glycine
Mutation, Missense
Cell Cycle Proteins
Biology
medicine.disease_cause
Protein Structure, Secondary
Catalysis
Conserved sequence
Inorganic Chemistry
Beta-propeller
Structural bioinformatics
Protein structure
medicine
Guanine Nucleotide Exchange Factors
Humans
Amino Acid Sequence
Cysteine
Motor Neuron Disease
Physical and Theoretical Chemistry
Binding site
Peptide sequence
Gene
Genetics
Mutation
Sequence Homology, Amino Acid
Organic Chemistry
Nuclear Proteins
Protein Structure, Tertiary
Computer Science Applications
Computational Theory and Mathematics
Subjects
Details
- ISSN :
- 09485023 and 16102940
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular Modeling
- Accession number :
- edsair.doi.dedup.....318b42bc877f2810d2b3ffb7472de4f3