Actinin-associated LIM protein: identification of a domain interaction between PDZ and spectrin-like repeat motifs.

Abstract

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 alpha-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 alpha-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.

• Authors: H Xia, S T Winokur, W L Kuo, M R Altherr, D S Bredt
• Journal: The Journal of cell biology (J Cell Biol) Vol. 139 Issue 2 Pg. 507-15 (Oct 20 1997) ISSN: 0021-9525 [Print] United States
• PMID: 9334352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• LIM Domain Proteins
• Microfilament Proteins
• PDLIM3 protein, human
• Pdlim3 protein, rat
• Actinin
• Spectrin

Topics

• Actinin (metabolism)
• Amino Acid Sequence
• Animals
• Base Sequence
• Binding Sites
• Cell Line
• Chromosome Mapping
• Chromosomes, Human, Pair 4
• Genetic Variation
• Humans
• Karyotyping
• LIM Domain Proteins
• Microfilament Proteins (biosynthesis, chemistry, genetics)
• Molecular Sequence Data
• Muscle, Skeletal (metabolism)
• Polymerase Chain Reaction
• Sequence Alignment
• Sequence Homology, Amino Acid
• Spectrin (chemistry)