title: Analysis of the interaction between the eukaryotic chaperonin CCT and its substrates actin and tubulin.
abstract: Two mechanisms have thus far been characterized for the assistance by chaperonins of the folding of other proteins. The first and best described is that of the prokaryotic chaperonin GroEL, which interacts with a large spectrum of proteins. GroEL uses a nonspecific mechanism by which any conformation of practically any unfolded polypeptide interacts with it through exposed, hydrophobic residues. ATP binding liberates the substrate in the GroEL cavity where it is given a chance to fold. A second mechanism has been described for the eukaryotic chaperonin CCT, which interacts mainly with the cytoskeletal proteins actin and tubulin. Cryoelectron microscopy and biochemical studies have revealed that both of these proteins interact with CCT in quasi-native, defined conformations. Here we have performed a detailed study of the docking of the actin and tubulin molecules extracted from their corresponding CCT:substrate complexes obtained from cryoelectron microscopy and image processing to localize certain regions in actin and tubulin that are involved in the interaction with CCT. These regions of actin and tubulin, which are not present in their prokaryotic counterparts FtsA and FtsZ, are involved in the polymerization of the two cytoskeletal proteins. These findings suggest coevolution of CCT with actin and tubulin in order to counteract the folding problems associated with the generation in these two cytoskeletal protein families of new domains involved in their polymerization.
authors.affiliation: Centro Nacional de Biotecnología, C.S.I.C., Campus Universidad Autónoma de Madrid, 28049, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Llorca
authors.forename: J
authors.initials: J
authors.lastname: Martín-Benito
authors.forename: P
authors.initials: P
authors.lastname: Gómez-Puertas
authors.forename: M
authors.initials: M
authors.lastname: Ritco-Vonsovici
authors.forename: K R
authors.initials: KR
authors.lastname: Willison
authors.forename: J L
authors.initials: JL
authors.lastname: Carrascosa
authors.forename: J M
authors.initials: JM
authors.lastname: Valpuesta
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D002417:Cattle; D020285:Cryoelectron Microscopy; D003598:Cytoskeletal Proteins; D005057:Eukaryotic Cells; D006801:Humans; D021621:Imaging, Three-Dimensional; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D016415:Sequence Alignment; D013379:Substrate Specificity; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D056427:t-Complex Genome Region
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C065103:FtsA protein, Bacteria; C071525:FtsZ protein, Bacteria; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D014404:Tubulin; C116196:PPP1R11 protein, human; D044767:Ubiquitin-Protein Ligases