The assumed model helps clarify to what extent the hydrophobicity distribution may help, support or even direct the protein folding. The question may be asked, how do these proteins become folded? How do they influence the substrate folding?Īn attempt to find answers to these questions on the basis of the “fuzzy oil drop” model has been undertaken and is presented in this paper. The object of the analysis was the chaperonin used as an example to search for possible mechanisms for the generation of such large constructions with a nano-machine character. Each part is responsible for a specific element of this algorithm. The mechanism of ATP binding and its collaboration with internal structural changes in cis- (called chains A-G in this paper) and trans-rings (chains H-N in this paper) reveals the functioning algorithm of the folding machine. The symmetric (7-fold) rings of GroEL interact with the co-chaperonin GroES. Chaperonin exists as a back-to-back linked double-ring complex. Only a certain subset of cellular proteins undergo the folding process accompanied by the chaperonins, which are large protein constructs which directly facilitate the protein folding process with participation of ATP molecules. Molecular chaperones are the proteins which bind and stabilize unfolded or partially folded proteins, thereby preventing them from being degraded. It has been discovered that the protein folding process is guided by additional molecules directing the structural changes toward the correct native form. Its possible influence on substrate folding is suggested. The hydrophobic force field structure generated by the chaperonin capsule is presented. The observed discrepancy between these two distributions seems to be aim-oriented, determining the structure-to-function relation. The empirically observed distribution of hydrophobic residues is confronted with the theoretical one representing the idealized hydrophobic core with hydrophilic residues exposure on the surface. The specific axial symmetry GroEL structure (two rings of seven units stacked back to back - 524 aa each) and the GroES (single ring of seven units - 97 aa each) polypeptide chains are analyzed using the hydrophobicity distribution expressed as excess/deficiency all over the molecule to search for structure-to-function relationships. The proteins of this group assist protein folding supported by ATP. These results identify a new role for the apical domains in coordinating client capture and progression through the cycle, and suggest a conserved mechanism of group I chaperonin function.The multi sub-unit protein structure representing the chaperonins group is analyzed with respect to its hydrophobicity distribution. Client is then fully encapsulated in mtHsp60/mtHsp10, revealing prominent contacts at two discrete sites that potentially support maturation. We further identify a striking asymmetric arrangement of the apical domains in the ATP state, in which an alternating up/down configuration positions interaction surfaces for simultaneous recruitment of mtHsp10 and client retention. Unexpectedly, client density is identified in all states, revealing interactions with mtHsp60’s apical domains and C-termini that coordinate client positioning in the folding chamber. Here, we determined cryo-electron microscopy (cryo-EM) structures of a hyperstable disease-associated mtHsp60 mutant, V72I, at three stages in this cycle. Despite its essential role in mitochondrial proteostasis, structural insights into how this chaperonin binds to clients and progresses through its ATP-dependent reaction cycle are not clear. The mitochondrial chaperonin, mtHsp60, promotes the folding of newly imported and transiently misfolded proteins in the mitochondrial matrix, assisted by its co-chaperone mtHsp10.
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