Structural and functional analysis of ataxin-2 and ataxin-3.

Abstract

Spinocerebellar ataxia types 2 (SCA2) and 3 (SCA3) are autosomal-dominantly inherited, neurodegenerative diseases caused by CAG repeat expansions in the coding regions of the genes encoding ataxin-2 and ataxin-3, respectively. To provide a rationale for further functional experiments, we explored the protein architectures of ataxin-2 and ataxin-3. Using structure-based multiple sequence alignments of homologous proteins, we investigated domains, sequence motifs, and interaction partners. Our analyses focused on presumably functional amino acids and the construction of tertiary structure models of the RNA-binding Lsm domain of ataxin-2 and the deubiquitinating Josephin domain of ataxin-3. We also speculate about distant evolutionary relationships of ubiquitin-binding UIM, GAT, UBA and CUE domains and helical ANTH and UBX domain extensions.

• Authors: Mario Albrecht, Michael Golatta, Ullrich Wüllner, Thomas Lengauer
• Journal: European journal of biochemistry (Eur J Biochem) Vol. 271 Issue 15 Pg. 3155-70 (Aug 2004) ISSN: 0014-2956 [Print] England
• PMID: 15265035 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ataxins
• Nerve Tissue Proteins
• Nuclear Proteins
• Peptides
• Proteins
• Repressor Proteins
• Ubiquitin
• polyglutamine
• RNA
• ATXN3 protein, human
• Ataxin-3

Topics

• Amino Acid Sequence
• Animals
• Ataxin-3
• Ataxins
• Humans
• Models, Molecular
• Molecular Sequence Data
• Nerve Tissue Proteins (chemistry, metabolism)
• Nuclear Proteins
• Peptides (chemistry, metabolism)
• Protein Binding
• Protein Structure, Tertiary
• Proteins (chemistry, metabolism)
• RNA (metabolism)
• Repressor Proteins
• Sequence Alignment
• Structure-Activity Relationship
• Ubiquitin (metabolism)