title: Dynamics, flexibility, and allostery in molecular chaperonins.
abstract: The chaperonins are a family of molecular chaperones present in all three kingdoms of life. They are classified into Group I and Group II. Group I consists of the bacterial variants (GroEL) and the eukaryotic ones from mitochondria and chloroplasts (Hsp60), while Group II consists of the archaeal (thermosomes) and eukaryotic cytosolic variants (CCT or TRiC). Both groups assemble into a dual ring structure, with each ring providing a protective folding chamber for nascent and denatured proteins. Their functional cycle is powered by ATP binding and hydrolysis, which drives a series of structural rearrangements that enable encapsulation and subsequent release of the substrate protein. Chaperonins have elaborate allosteric mechanisms to regulate their functional cycle. Long-range negative cooperativity between the two rings ensures alternation of the folding chambers. Positive intra-ring cooperativity, which facilitates concerted conformational transitions within the protein subunits of one ring, has only been demonstrated for Group I chaperonins. In this review, we describe our present understanding of the underlying mechanisms and the structure-function relationships in these complex protein systems with a particular focus on the structural dynamics, allostery, and associated conformational rearrangements.
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway. Electronic address: lars.skjarven@uib.no.
authors.forename: Lars
authors.initials: L
authors.lastname: Skjærven
authors.affiliation: Department of Macromolecular Structure, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cuellar
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Aurora
authors.initials: A
authors.lastname: Martinez
authors.affiliation: Department of Macromolecular Structure, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Valpuesta
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000494:Allosteric Regulation; D018833:Chaperonins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D016000:Cluster Analysis; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D018583:Pliability; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D000255:Adenosine Triphosphate; D018833:Chaperonins
keywords: Allostery; Chaperone; Chaperonin; Conformational changes; Protein dynamics; Protein folding