Actinin-associated LIM Protein: Identification of a Domain Interaction between PDZ and Spectrin-like Repeat Motifs
| Autor: | Sara T. Winokur, Wen-Lin Kuo, Michael R. Altherr, David S. Bredt, Houhui Xia |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
musculoskeletal diseases
Molecular Sequence Data PDZ domain Sequence alignment Actinin Polymerase Chain Reaction Article Cell Line medicine Animals Humans Spectrin Amino Acid Sequence Muscular dystrophy Muscle Skeletal Peptide sequence Syntrophin Binding Sites Base Sequence Sequence Homology Amino Acid biology Microfilament Proteins Chromosome Mapping Genetic Variation Cell Biology LIM Domain Proteins musculoskeletal system medicine.disease Molecular biology Cell biology Karyotyping biology.protein Chromosomes Human Pair 4 Dystrophin Sequence Alignment |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | PDZ motifs are protein–protein interaction domains that often bind to COOH-terminal peptide sequences. The two PDZ proteins characterized in skeletal muscle, syntrophin and neuronal nitric oxide synthase, occur in the dystrophin complex, suggesting a role for PDZ proteins in muscular dystrophy. Here, we identify actinin-associated LIM protein (ALP), a novel protein in skeletal muscle that contains an NH2-terminal PDZ domain and a COOH-terminal LIM motif. ALP is expressed at high levels only in differentiated skeletal muscle, while an alternatively spliced form occurs at low levels in the heart. ALP is not a component of the dystrophin complex, but occurs in association with α-actinin-2 at the Z lines of myofibers. Biochemical and yeast two-hybrid analyses demonstrate that the PDZ domain of ALP binds to the spectrin-like motifs of α-actinin-2, defining a new mode for PDZ domain interactions. Fine genetic mapping studies demonstrate that ALP occurs on chromosome 4q35, near the heterochromatic locus that is mutated in fascioscapulohumeral muscular dystrophy. |
| Databáze: | OpenAIRE |
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