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Biomedical subjects

M A Basharov

Publications and source records attributed to M A Basharov.

14 recordsLinked to original sources
PubMed2000

Cotranslational folding of proteins.

We suppose that folding of proteins occurs cotranslationally by the following scheme. The polypeptide chains enter the folding sites from protein translocation complexes (ribosome, translocation machinery incorporated in membranes) directionally with the N-terminus and gradually. The chain starts to fold as soon as its N-terminal residue enters the folding site from the translocation complex. The folding process accompanies the translocation of the chain to its folding site and is completed after the C-terminal residue leaves the translocation complex. Proteins fold in sequential stages, by translocation of their polypeptide into folding compartments. At each stage a particular conformation of the N-terminal part of the chain that has emerged from the translocation complex is formed. The formation of both the particular conformations of the N-terminal chain segment at each folding stage and the final native protein conformation at the last stage occurs in a time that does not exceed the duration of the fastest elongation cycle on the ribosome.

Cell Membrane↗
PubMed2000

The posttranslational concept of protein folding: how valid is it?

Two concepts of protein folding are known. One of them, the cotranslational concept, states that a protein folds during the synthesis of the polypeptide chain on the ribosome. According to the other, the posttranslational concept, the protein starts to fold just after the synthesis of its polypeptide chain. This article attempts to show that the posttranslational concept is hardly suited to solve the problem of protein folding. In our opinion, polypeptide chains cannot be represented as random coils. They are stiff chain-like macromolecules rather than flexible ones: the single bond rotational barriers of a polypeptide substantially exceed the accepted standard values; even in strong denaturing conditions, a protein possesses a considerable amount of residual folded structures. We believe that the popular "hierarchical" models for the protein folding mechanism are not realistic because the formation of secondary and tertiary structures of proteins occurs simultaneously and cooperatively. The time for the elongation of a polypeptide chain by one amino acid residue during biosynthesis exceeds considerably the time of the formation of alpha-helices and beta-sheets in proteins as well as the time supposed for the spatial structure formation of a native protein during renaturation. Thus, we believe that the mechanism of protein folding in vivo cannot be clarified by denaturation-renaturation experiments. In our opinion, the phenomenon of protein renaturation is no more than the restoration of native protein conformation (which initially forms cotranslationally) disrupted during denaturation, and thus denaturation-renaturation experiments cannot serve as a model to clarify the mechanism of protein folding.

Models, Chemical↗
PubMed1997

Role of chaperonins in protein folding. A new model of the GroEL/GroES complex architecture.

Polypeptide chain folds to native protein under physiological conditions. At least in vivo, in addition to physiological conditions, certain initial kinetic conditions are also required upon folding. These non-physiological conditions specify that amino acid residues of a polypeptide chain move to the folding place directionally beginning from the first N-terminal residue, sequentially one after another, and gradually one-by-one. Chaperonin complex provides in the cell for the initial kinetic requirements for co-translational folding of polypeptide chain to native protein in sites in the cytoplasm distant from the ribosome and in the plasma of organelles. A new model of the GroEL/GroES complex architecture is proposed using structural data on the GroEL and GroES chaperonins. The known models of the chaperonin complex structure suggest that it is formed by binding of a dome-like GroES oligomer to the end orifice of the GroEL cylinder via long mobile loops of its base. According to the new model, to form the complex two GroES oligomers one-by-one enter with their roofing, i.e., in an inverted way, into the GroEL cylinder and orifices and lock them. The proposed complex has the form of coaxial cylinders. It is sufficiently stable and cannot dissociate under physiological conditions. The complex becomes functionally active when it binds the incoming substrate polypeptide. An active GroEL/GroES complex resembles a hollow cylinder with end orifices. The diameter of the cavity and orifices is about 30 A.

Chaperonin 10↗
PubMedDate not supplied

Protein folding.

The problem of protein folding is that how proteins acquire their native unique three-dimensional structure in the physiological milieu. To solve the problem, the following key questions should be answered: do proteins fold co- or post-translationally, i.e. during or after biosynthesis, what is the mechanism of protein folding, and what is the explanation for fast folding of proteins? The two first questions are discussed in the current review. The general lines are to show that the opinion, that proteins fold after they are synthesized is hardly substantiated and suitable for solving the problem of protein folding and why proteins should fold cotranslationally. A possible tentative model for the mechanism of protein folding is also suggested. To this end, a thorough analysis is made of the biosynthesis, delivery to the folding compartments, and the rates of the biosynthesis, translocation and folding of proteins. A cursory attention is assigned to the role of GroEL/ES-like chaperonins in protein folding.

Protein Biosynthesis↗
PubMedDate not supplied

[Are synthetic proteins relevant to the problem of protein folding?].

The possibility to derive the analogs of native proteins by the chemical synthesis is considered to be a serious argument for the concept of posttranslational protein folding. The present paper analyzes for the first time chemically synthesized proteins to reveal whether they are relevant to the problem of protein folding. The results enable the following conclusions to be drawn. The acquisition of the peculiar conformations by the chemically synthesized proteins to exhibit the specific functions is conditioned by the highly marked features of the secondary and tertiary structures of the corresponding native proteins. These features will make themselves evident only if favorable conditions are carefully chosen during the experiments for each individual protein. Thus, in our opinion, the possibility to derive a synthetic protein is hardly evidence for the posttranslational folding of proteins.

Protein Biosynthesis↗
PubMedDate not supplied

[Various views on the formation of the spatial structure of proteins].

Basing on the protein tertiary structure data analysis, the peculiarities of enzymatic catalysis, as well as on the results of ab initio conformational energy map calculations of dipeptides, the conclusion is drawn, that the synthesis of polypeptide chains on the ribosome occurs on the right hand conformation of amino acid residues. For the number of amino acid residues to transfer to left hand conformation, local and electoral conditions are necessary. Some possible errors in the X-ray crystal structure data of proteins are pointed out.

Amino Acids↗
PubMedDate not supplied

[The effect of side radicals on the peptide structure. Surface of potential energy of model alanine and phenylalanine dipeptides].

The problem of stabilization of different dipeptide conformations is discussed within the fragment-fragment interactions method. It is shown, that the introduction of a CH3-group in glycine is a weak perturbation and for Ala-dipeptide the preferential structure remains C7 (like for glycine). On the contrary the introduction of a C6H5CH2-group in glycine is a strong perturbation and for Phe-dipeptide C5 becomes the preferential structure.

Alanine↗
PubMedDate not supplied

[Stability of the alpha-helix structure of oligopeptides].

The problem of stabilization of oligopeptide alpha-helix conformation is discussed. The stabilizing role of intramolecular H-bonds and coulombic interactions for single molecules was shown. The influence of media results in the competition for formation of inter and intramolecular H-bonds and for coulombic interactions. High competitive media, eg. water, diminishes alpha-helix stability.

Electricity↗
PubMedDate not supplied

[Surface potential energy of peptides and conformation of amino acid residues in proteins. Preliminary results of processing using databank protein structures].

The fact of enzymatic synthesis of a protein polypeptide chain have been mentioned. The potential energy surfaces of peptides have been analysed. Based on the obtained results and characteristic peculiarity of the enzymatic reactions have been concluded that the non-glycine residues in a three-dimensional (3-D) protein structure most likely should be in the negative conformations. The analysis of the amino acid residue conformations have been performed on the 185 3-D protein structures obtained by the X-ray crystallography at high resolution. It has been shown that the changes in the protein surrounding environment, in crystalline forms and functional state of protein, bindings of the ligands and inhibitors do not lead to the changes in the polarity of non-glycine residues conformational angles phi, and in the polarity of the conformational angles omega of all residues. Based on the results, 81 independent protein structures have been selected. The preliminary results of analysis of glycine and non-glycine residue conformations occurring in these structures have been presented.

Amino Acids↗
PubMedDate not supplied

[Distribution of amino acid residue conformation in three-dimensional protein structures. Analysis of the non-glycine residues in "positive" conformations].

The analysis of amino acid residue conformations occurring in 81 three-dimensional (3-D) X-ray protein structures have been made. It has been revealed that a relatively great number of non-glycine residues in positive conformation may be considered as a simple criterion pointing to the presence at least of local errors in the structure. The number of 3-D protein structures have been specified, that contains some local errors. Based on the literature data analysis results, and on the results of residue molecular geometry analysis, it has been shown that many of the non-glycine residues in positive conformations have a poorly determined atomic coordinates: they are involved in the ill determined segments of the polypeptide chains, or display a higher or high temperature factor. Some of the others left-handed non-glycine residues have a non-rigid molecular geometry, or are in the energetically unfavorable conformations. Based on the obtained results, made the assumption that the non-glycine residues in a 3-D protein structure should be occur only in the negative conformations.

Amino Acids↗