title: The crystal structure of dynein intermediate chain-light chain roadblock complex gives new insights into dynein assembly.
abstract: The roadblock/LC7 dynein light chain is a ubiquitous component of all dyneins and is essential for many diverse processes including proper axonal transport and dendrite growth. In addition, LC7 functions in non-dynein transcriptional activation of the transforming growth factor-beta complex. Crystal structures of Drosophila melanogaster LC7 in the apo form and in complex with a segment of the disordered N-terminal domain of dynein intermediate chain (IC) provide the first definitive identification of the IC sequence recognized by LC7. The site, confirmed by isothermal titration calorimetry studies, overlaps the IC sequence considered in the literature to be an IC self-association domain. The IC peptide binds as two amphipathic helices that lie along an extensive hydrophobic cleft on LC7 and ends with a polar side-chain interaction network that includes conserved residues from both proteins. The LC7 recognition sequence on IC and its interface with LC7 are well conserved and are, thus, likely representative of all IC x LC7 structures. Interestingly, the position of bound IC in the IC x LC7 complex mimics a helix that is integrated into the primary structure in distantly related LC7 homologs. The IC x LC7 structure further shows that the naturally occurring robl(Z) deletion mutation contains the majority of the IC binding site and suggests that promotion of IC binding by phosphorylation of LC7 is an indirect effect.
authors.affiliation: Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Hall
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Song
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Karplus
authors.forename: Elisar
authors.initials: E
authors.lastname: Barbar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002151:Calorimetry; D002352:Carrier Proteins / Q000737:chemistry*; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry*; D004331:Drosophila melanogaster / Q000378:metabolism*; D004398:Dyneins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D001059:Apoproteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; C120447:robl protein, Drosophila; D004398:Dyneins
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