title: Crystal structure of dynein light chain TcTex-1.
abstract: TcTex-1, one of three dynein light chains of the dynein motor complex, has been implicated in targeting and binding cargoes to cytoplasmic dynein for retrograde or apical transport. Interactions between TcTex-1 and a diverse set of proteins such as the dynein intermediate chain, Fyn, DOC2, FIP1, the poliovirus receptor, CD155, and the rhodopsin cytoplasmic tail have been reported; yet, despite the broad range of targets, a consensus binding sequence remains uncertain. Consequently, we have solved the crystal structure of the full-length Drosophila homolog of TcTex-1 to 1.7 A resolution using MAD phasing to gain insight into its function and target specificity. The structure is homodimeric with a domain swapping of beta-strand 2 and has a fold similar to the dynein light chain, LC8. Based on structural alignment, the TcTex-1 and LC8 sequences show no identity, although the root mean square deviation between secondary structural elements is less than 1.6 A. Moreover, the N terminus, which is equivalent to beta-strand 1 in LC8, is splayed out and binds to a crystallographic dimer as an anti-parallel beta-strand at the same position as the neuronal nitric-oxide synthase peptide in the LC8 complex. Similarity to LC8 and comparison to the LC8-neuronal nitricoxide synthase complex suggest that TcTex-1 binds its targets in a similar manner as LC8 and provides insight to the lack of strict sequence identity among the targets for TcTex-1.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Williams
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Hendrickson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry*; D004398:Dyneins; D020224:Expressed Sequence Tags; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry; D008869:Microtubule-Associated Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry; D012243:Rhodopsin / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D056427:t-Complex Genome Region
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D008024:Ligands; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D011991:Receptors, Virus; C542608:ctp protein, Drosophila; C066100:poliovirus receptor; D012243:Rhodopsin; D004398:Dyneins