Key result
The internal region of ALP is largely unstructured but functional, and the ZM motif defines part of the interaction surface between ALP and the α-actinin rod domain.
Does not inform clinical decisions; extends molecular mapping of ALP–α-actinin interactions for future mechanistic studies.
BACKGROUND: The PDZ-LIM proteins are a family of signalling adaptors that interact with the actin cross-linking protein, alpha-actinin, via their PDZ domains or via internal regions between the PDZ and LIM domains. Three of the PDZ-LIM proteins have a conserved 26-residue ZM motif in the internal region, but the structure of the internal region is unknown. RESULTS: In this study, using circular dichroism and nuclear magnetic resonance (NMR), we showed that the ALP internal region (residues 107-273) was largely unfolded in solution, but was able to interact with the alpha-actinin rod domain in vitro, and to co-localize with alpha-actinin on stress fibres in vivo. NMR analysis revealed that the titration of ALP with the alpha-actinin rod domain induces stabilization of ALP. A synthetic peptide (residues 175-196) that contained the N-terminal half of the ZM motif was found to interact directly with the alpha-actinin rod domain in surface plasmon resonance (SPR) measurements. Short deletions at or before the ZM motif abrogated the localization of ALP to actin stress fibres. CONCLUSION: The internal region of ALP appeared to be largely unstructured but functional. The ZM motif defined part of the interaction surface between ALP and the alpha-actinin rod domain.
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Klaavuniemi et al. (2009) studied this question. ALP107-273 protein fragment was evaluated on Protein-protein interaction affinity (Kd). The internal region of ALP is largely unstructured but functional, and the ZM motif defines part of the interaction surface between ALP and the α-actinin rod domain.
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