Molecular chaperones in protein folding and translocation

Current Opinion in Structural Biology

Volumn 6, Issue 1, 1996, Pages 43-50

  Clarke, Anthony R ^a  

^a SCHOOL OF MEDICAL SCIENCES   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; CARRIER PROTEIN; CHAPERONE; CHAPERONIN; HEAT SHOCK PROTEIN; HEAT SHOCK PROTEIN 70;

BINDING SITE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN BINDING; PROTEIN FOLDING; PROTEIN PROTEIN INTERACTION; PROTEIN TRANSPORT; REVIEW;

EID: 0029864380     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-440X(96)80093-5     Document Type: Article

References (73)

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40. Buchberger A, Schroder H, Buttner M, Valencia A, Bukau B: A conserved loop in the ATPase domain of the DnaK chaperone is essential for stable binding of GrpE Nature Struct Biol 1994, 1:95-101. Deletion analysis identifies a surface loop near the nucleotide-binding site of DnaK as a determinant of GrpE binding. Conservation of this loop throughout the hsp70 family suggests a widespread requirement for exchange factors.
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57. Bochkareva ES, Girshovich AS: ATP induces non-identity of two rings in chaperonin GroEL. J Biol Chem 1994, 269:23869-23871. ADP inhibition of the ATPase reaction shows two phases, implying asymmetry in nucleotide binding.
58. Yifrach O, Horovitz A: Two lines of allosteric communication in the oligomeric chaperonin GroEL are revealed by the single mutation Arg196→Ala. J Mol Biol 1994, 243:397-401.
59. Yifrach O, Horovitz A: Nested co-operativity in the ATPase activity of the oligomeric chaperonin GroEL. Biochemistry 1995, 34:5303-5308. These papers [58,59] are central to the understanding of the unusual cooperativity of cpn60. The authors use steady-state kinetic methods to define the positive (intra-ring) and negative (inter-ring) cooperativity of cpn60 with respect to ATP binding.
60. Burston SG, Ranson NA, Clarke AR: The origins and consequences of asymmetry in the chaperonin reaction cycle. J Mol Biol 1995, 249:138-152. Transient kinetics and equilibrium binding are used to examine the induction of asymmetry in the cpn60 structure and the dynamics of the co-protein interaction.
61. Murai N, Taguchi H, Yoshida M: Kinetic analysis of the interaction between GroEL and reduced α-lactalbumin effects of GroES and nucleotides. J Biol Chem 1995, 270:19957-19963. An extensive, time-resolved study of protein-protein interactions in the chaperonin system. The dissociation constant for the substrate (∼1 nM) is increased by three orders of magnitude by ATP binding. The authors identify two classes of ADP sites (arising through negative cooperativity) and conclude that only low-affinity binding influences the interaction with the protein substrate.
62. Horowitz PM, Hua S, Gibbons DL: Hydrophobic surfaces that are hidden in chaperonin-60 can be exposed by formation of assembly-competent monomers or by ionic perturbation of the oligomer. J Biol Chem 1995, 270:1535-1542.
63. Gorovits BM, Horowitz PM: The molecular chaperonin cpn60 displays local flexibility that is reduced after binding with an unfolded peptide. J Biol Chem 1995, 270:13057-13062. These papers [62,63] demonstrate the flexibility of the substrate-binding domains of cpn60 and discuss the functional relationship between chaperone mobility and activity.
64. Fenton WA, Kashi Y, Furtak K, Horwich AL: Residues in chaperonin GroEL required for polypeptide binding and release. Nature 1994, 371:614-619. A comprehensive and illuminating mutagenic study, which maps out the nucleotide-, co-protein (cpn10)- and substrate-binding sites on the cpn60 oligomer in relation to the crystallographically determined structure.
65. Schmidt M, Rutkat K, Rachel R, Pfeifer G, Jaenicke R, Viitanen PV, Lorimer GH, Buchner J: Symmetric complexes of GroE chaperonins as part of the functional cycle. Science 1994, 265:656-659. Electron microscopy shows that, whereas ADP induces one-sided binding of cpn10 to cpn60, ATP or analogues can induce the formation of symmetric complexes containing two co-proteins. The possibility that this latter structure is an obligatory intermediate in the chaperonin reaction cycle is discussed.
66. Llorca O, Marco S, Carrascosa JL, Valpuesta JM: The formation of symmetrical GroEL-GroES complexes in the presence of ATP. FEBS Lett 1994, 345:181-186. The results presented agree with those in [64•], except that ATP analogues are not seen to support the formation of the symmetric complexes.
67. Schmidt M, Buchner J, Todd MJ, Lorimer GH, Viitanen PV: On the role of GroES in the chaperonin-assisted folding reaction: three case studies. J Biol Chem 1994, 269:10304-10311. Two important aspects of assisted folding are demonstrated. Firstly, proteins with completely different topologies can be refolded by chaperonins, and secondly, the requirement for cpn10 depends on the folding conditions as well as the intrinsic properties of the polypeptide chains.
68. Staniforth RA, Cortés A, Burston SG, Atkinson T, Holbrook JJ, Clarke AR: The stability and hydrophobicity of cytosolic and mitochondrial malate dehydrogenases and their relation to chaperonin-assisted folding. FEBS Lett 1994, 344:129-135. A study of two homologous proteins which show very different responses to chaperonins. It is demonstrated that the physico-chemical properties of the protein chain influence the observed mechanism of a chaperonin-assisted reaction as much as the properties of the chaperonin itself.
69. Weissman JS, Hohl CM, Kovalenko O, Kashi Y, Chen S, Braig K, Saibil HR, Fenton WA, Horwich AL: Mechanism of GroEL action: productive release of polypeptide from a sequestered position under GroES. Cell 1994, 83:577-587. A convincing demonstration that a substrate protein can be bound at the open end of GroEL (opposite to GroES) or at the capped end (trapped under GroES). Their experiments suggest a two-step mechanism in which GroES displaces the polypeptide from an initial open binding site to sequester it within a GroES-enclosed cavity.
70. Peralta D, Hartman DJ, Hoogenraad NJ, Hoj PB: Generation of a stable folding intermediate which can be rescued by the chaperonins GroEL and GroES. FEBS Lett 1994, 339:45-49. A key paper in the field, which shows that over a given range of temperatures mitochondrial malate dehydrogenase folds to a trapped, metastable state. The addition of chaperon in re-initiates folding to the native state. Crucially, the experiment shows that the chaperonin has an active role in releasing kinetically trapped structures, rather than merely serving as an Anfinsen cage for the spontaneous process.
71. Ranson NA, Dunster NJ, Burston SG, Clarke AR: Chaperonins can catalyse the reversal of early aggregation steps when a protein misfolds. J Mol Biol 1995, 250:581-586. The kinetics of chaperonin-assisted folding and spontaneous misfolding of mitochondrial malate dehydrogenase show that misfolding proceeds by a two-phase aggregation. Small, rapidly formed aggregates very slowly go through a second phase of aggregation/consolidation. Chaperonins break contacts in the small early aggregates to supply the folding pathway with competent monomers, but they cannot rescue the late, consolidated aggregates. In this reaction, chaperonins are effective at substoichiometric concentrations and increase both the rate and yield of mitochondrial malate dehydrogenase folding. By these criteria, they behave as catalysts of folding by disrupting trapped states.
72. Fisher MT: The effect of GroES on the GroEL-dependent assembly of dodecameric glutamine synthetase in the presence of ATP and ADP. J Biol Chem 1994, 269:13629-13636. A careful and convincing study of the chaperonin-dependent assembly pathway of this large structure. The experiments map the steps in subunit assembly and analyze the lag times for refolding when the stable cpn60-substrate (monomer) complex is activated for refolding by different ligand combinations.
73. Fisher MT, Yuan XS: The rates of commitment renaturation of rhodanese and glutamine synthetase in the presence of the GroE chaperonins. J Biol Chem 1994, 269:29598-29601. The refolding reaction of a monomeric and a multimeric protein are used to determine at what point in the pathways these substrates become chaperonin independent. The chaperonins are removed by antibody precipitation at different folding times and the results show that rhodanese (monomer) is committed at the rate of regain of activity whereas the oligomeric enzyme is committed before the appearance of activity.