Structural aspects of GroEl function

Horovitz, Amnon

doi:10.1016/s0959-440x(98)80015-8

Cited by 58 publications

(27 citation statements)

References 76 publications

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“…Recently (Yifrach and Horovitz, 1998), we measured the values of Hill coefficients, with respect to ATP, for a series of mutants of the allosteric tetradecameric chaperonin GroEL (Fenton and Horwich, 1997;Horovitz, 1998), using both steadystate and transient kinetic methods. An excellent linear correlation with a slope of 0.89 (±0.08) was found between values of Hill coefficients determined for steady-state data (n steady-state ) from fits to equation (1) and those determined for transient kinetic data (n transient ) from fits to equation (2).…”

Section: Society For Mathematical Biologymentioning

confidence: 99%

On the Relationship Between the Hill Coefficients for Steady-state and Transient Kinetic Data: A Criterion for Concerted Transitions in Allosteric Proteins

Horovitz

2000

Bulletin of Mathematical Biology

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A frequently used measure for the extent of cooperativity in ligand binding by allosteric proteins is the Hill coefficient. Hill coefficients can be measured for steady-state kinetic data and also for transient kinetic data. Here, the relationship between the two types of Hill coefficients is analysed. It is shown that a value of 1 for the ratio of the two Hill coefficients is a test for a concerted ligand-induced transition between two conformations of the protein, in accordance with the Monod-Wyman-Changeux model. A value of 1 for this ratio has recently been observed for a series of chaperonin GroEL mutants suggesting that ATP-induced allosteric transitions in this protein are concerted.

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Section: Society For Mathematical Biologymentioning

confidence: 99%

On the Relationship Between the Hill Coefficients for Steady-state and Transient Kinetic Data: A Criterion for Concerted Transitions in Allosteric Proteins

Horovitz

2000

Bulletin of Mathematical Biology

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“…Protein-folding machinery in Escherichia coli includes chaperonin GroEL and it's cochaperonin GroES, which facilitates folding of a variety of proteins by binding nonnative conformations in the hydrophobic cavity of an open GroEL ring and then triggering productive folding on subsequent binding of GroES and adenosine triphosphate (ATP) to the same ring as polypeptide (Horvitz 1998;Sigler et al 1998) or to the opposite ring (Chaudhuri et al 2001). A polypeptide substrate forms its association with GroEL through multivalent hydrophobic contacts inside the central cavity of a ring.…”

Section: Introductionmentioning

confidence: 99%

Factors governing the substrate recognition by GroEL chaperone: a sequence correlation approach

Chaudhuri

Gupta

2005

Cell Stress Chaper

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The chaperonin GroEL binds to a large number of polypeptides, prevents their self-association, and mediates appropriate folding in a GroES and adenosine triphosphate-dependent manner. But how the GroEL molecule actually recognizes the polypeptide and what are the exact GroEL recognition sites in the substrates are still poorly understood. We have examined more than 50 in vivo substrates as well as well-characterized in vitro substrates, for their binding characteristics with GroEL. While addressing the issue, we have been driven by the basic concept that GroES, being the cochaperonin of GroEL, is the best-suited substrate for GroEL, as well as by the fact that polypeptide substrate and GroES occupy the same binding sites on the GroEL apical domain. GroES interacts with GroEL through selective hydrophobic residues present on its mobile loop region, and we have considered the group of residues on the GroES mobile loop as the key element in choosing a substrate for GroEL. Considering the hydrophobic region on the GroES mobile loop as the standard, we have attempted to identify the homologous region on the peptide sequences in the proteins of our interest. Polypeptides have been judged as potential GroEL substrates on the basis of the presence of the GroES mobile loop-like hydrophobic segments in their amino acid sequences. We have observed 1 or more GroES mobile loop-like hydrophobic patches in the peptide sequence of some of the proteins of our interest, and the hydropathy index of most of these patches also seems to be approximately close to that of the standard. It has been proposed that the presence of hydrophobic patches having substantial degree of hydropathy index as compared with the standard segment is a necessary condition for a peptide sequence to be recognized by GroEL molecules. We also observed that the overall hydrophobicity is also close to 30% in these substrates, although this is not the sufficient criterion for a polypeptide to be assigned as a substrate for GroEL. We found that the binding of aconitase, ␣-lactalbumin, and murine dihydrofolate reductase to GroEL falls in line with our present model and have also predicted the exact regions of their binding to GroEL. On the basis of our GroEL substrate prediction, we have presented a model for the binding of apo form of some proteins to GroEL and the eventual formation of the holo form. Our observation also reveals that in most of the cases, the GroES mobile loop-like hydrophobic patch is present in the unstructured region of the protein molecule, specifically in the loop or ␤-sheeted region. The outcome of our study would be an essential feature in identifying a potential substrate for GroEL on the basis of the presence of 1 or more GroES mobile loop-like hydrophobic segments in the amino acid sequence of those polypeptides and their location in three-dimensional space.

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“…The bacterial chaperonin GroEL and its cofactor GroES are among the best characterised molecular chaperones (Fenton & Horwich, 1997;Martin & Hartl, 1997;Horovitz, 1998). X-ray studies (Braig et al, 1994Boisvert et al, 1996;Xu et al, 1997) combined with electron microscopy (EM) studies (Langer et al, 1992;Ishii et al, 1992;Chen et al, 1994;Roseman et al, 1996;White et al, 1997) have provided insight into the functional cycle of this chaperonin.…”

Section: Introductionmentioning

confidence: 99%

Conformational changes in the chaperonin GroEL: new insights into the allosteric mechanism 1 1Edited by A. R. Fersht

Groot

Vriend

Berendsen

1999

Journal of Molecular Biology

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Conformational changes are known to play a crucial role in the function of the bacterial GroE chaperonin system. Here, results are presented from an essential dynamics analysis of known experimental structures and from computer simulations of GroEL using the CONCOORD method. The results indicate a possible direct form of inter-ring communication associated with internal¯uctuations in the nucleotide-binding domains upon nucleotide and GroES binding that are involved in the allosteric mechanism of GroEL. At the level of conformational transitions in entire GroEL rings, nucleotide-induced structural changes were found to be distinct and in principle uncoupled from changes occurring upon GroES binding. However, a coupling is found between nucleotide-induced conformational changes and GroES-mediated transitions, but only in simulations of GroEL double rings, and not in simulations of single rings. This provides another explanation for the fact that GroEL functions a double ring system.

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Structural aspects of GroEl function

Cited by 58 publications

References 76 publications

On the Relationship Between the Hill Coefficients for Steady-state and Transient Kinetic Data: A Criterion for Concerted Transitions in Allosteric Proteins

On the Relationship Between the Hill Coefficients for Steady-state and Transient Kinetic Data: A Criterion for Concerted Transitions in Allosteric Proteins

Factors governing the substrate recognition by GroEL chaperone: a sequence correlation approach

Conformational changes in the chaperonin GroEL: new insights into the allosteric mechanism 1 1Edited by A. R. Fersht

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