Solution structure of a ubiquitin-like domain from tubulin-binding cofactor B.
Proper folding and assembly of tubulin alphabeta-heterodimers involves a stepwise progression mediated by a group of protein cofactors A through E. Upon release of the tubulin monomers from the chaperonin CCT, they are acted upon by each cofactor in the folding pathway through a unique combination of protein interaction domains. Three-dimensional structures have previously been reported for cofactor A and the C-terminal CAP-Gly domain of cofactor B (CoB). Here we report the NMR structure of the N-terminal domain of Caenorhabditis elegans CoB and show that it closely resembles ubiquitin as was recently postulated on the basis of bioinformatic analysis (Grynberg, M., Jaroszewski, L., and Godzik, A. (2003) BMC Bioinformatics 4, 46). CoB binds partially folded alpha-tubulin monomers, and a putative tubulin-binding motif within the N-terminal domain is identified from sequence and structure comparisons. Based on modeling of the homologous cofactor E ubiquitin-like domain, we hypothesize that cofactors B and E may associate via their beta-grasp domains in a manner analogous to the PB1 and caspase-activated deoxyribonuclease superfamily of protein interaction domains.
Lytle
Betsy L
BL
Center for Eukaryotic Structural Genomics, Madison, Wisconsin 53706-1549, USA.
Peterson
Francis C
FC
Qiu
Shi-Hong
SH
Luo
Ming
M
Zhao
Qin
Q
Markley
John L
JL
Volkman
Brian F
BF
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014404:Tubulin / Q000737:chemistry*; D025801:Ubiquitin / Q000737:chemistry*
D029742:Caenorhabditis elegans Proteins; D008869:Microtubule-Associated Proteins; D011994:Recombinant Proteins; D014404:Tubulin; D025801:Ubiquitin; C494440:tbcb-1 protein, C elegans