Download MendeleyStructural basis of diverse sequence-dependent target recognition by the 8 kDa dynein light chain.
Fan, J., Zhang, Q., Tochio, H., Li, M., Zhang, M.(2001) J Mol Biol 306: 97-108
- PubMed: 11178896
- DOI: https://doi.org/10.1006/jmbi.2000.4374
- Primary Citation of Related Structures:
1F3C, 1F95, 1F96 - PubMed Abstract:
Dyneins are multi-subunit molecular motors that translocate molecular cargoes along microtubules. Other than acting as an essential component of the dynein motor complex, the 89-residue subunit of dynein light chain (DLC8) also regulates a number of other biological events by binding to various proteins and enzymes. Currently known DLC8 targets include neuronal nitric oxide synthase; the proapoptotic Bcl-2 family member protein designated Bim; a Drosophila RNA localization protein Swallow, myosin V, neuronal scaffolding protein GKAP, and IkappaBalpha, an inhibitor of the NFkappaB transcription factor. The DLC8-binding domains of the various targets are confined within a short, continuous stretch of amino acid residues. However, these domains do not share any obvious sequence homology with each other. Here, the three-dimensional structures of DLC8 complexed with two peptides corresponding to the DLC8-binding domains of neuronal nitric oxide synthase and Bim, respectively, were determined by NMR spectroscopy. Although the two DLC8-binding peptides have entirely different amino acid sequences, both peptides bind to the protein with a remarkable similar conformation by engaging the symmetric DLC8 dimer through antiparallel beta-sheet augmentation via the beta2 strand of the protein. Structural comparison indicates that the two target peptides use different regions within the conformational flexible peptide-binding channels to achieve binding specificity. We have also re-determined the apo-form solution structure of DLC8 in this work. The structures of the DLC8/target peptide complexes, together with the dynamic properties of the protein, provide a molecular basis of DLC8's diverse amino acid sequence-dependent target recognition.
Organizational Affiliation:
Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, Kowloon, P. R. China.
