Intracellular Protein Biosynthesis: A Review

Proteins are macromolecules made up of many amino acids that linked together by peptide bond to make a protein molecule. The sequence and the number of amino acids determines each protein unique structure and specific function. Proteins play a vital role in living systems and play important biological functions. Biosynthesis of protein occur in our body cells in order to support the biological function in our body. Intracellular protein synthesis is a complex process that involve the transformation of information and instructions from a genetic material DNA inside the nucleus to form mRNA molecules that transferred to the cytoplasm and liked to the cytoplasmic ribosome. Subsequently, the m RNA and further encode a sequence of amino acid in a specific order and number to form a polypeptide chains that finally undergoes conformational changes and folding to form a particular structure protein. This review will focus on the tow consecutive stages of protein biosynthesis; transcription and translation, and their substage processes; initiation, elongation, and termination. Briefly, overview the role of protein in the biological function and the different types of protein structure.

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Force transduction creates long-ranged coupling in ribosomes stalled by arrest peptides

10.1101/2020.10.16.342899 ◽

2020 ◽

Author(s):

Matthew H Zimmer ◽

Michiel JM Niesen ◽

Thomas F Miller

Keyword(s):

Amino Acids ◽

Secondary Structure ◽

Conformational Changes ◽

Protein Biosynthesis ◽

Essential Amino Acids ◽

Structural Features ◽

Applied Force ◽

Catalytic Center ◽

Force Propagation ◽

Force Transduction

AbstractForce-sensitive arrest peptides regulate protein biosynthesis by stalling the ribosome as they are translated. Synthesis can be resumed when the nascent arrest peptide experiences a pulling force of sufficient magnitude to break the stall. Efficient stalling is dependent on the specific identity of a large number of amino acids, including amino acids which are tens of angstroms away from the peptidyl transferase center (PTC). The mechanism of force-induced restart and the role of these essential amino acids far from the PTC is currently unknown. We use hundreds of independent molecular dynamics trajectories spanning over 120 μs in combination with kinetic analysis to characterize the barriers along the force-induced restarting pathway for the arrest peptide SecM. We find that the essential amino acids far from the PTC play a major role in controlling the transduction of applied force. In successive states along the stall-breaking pathway, the applied force propagates up the nascent chain until it reaches the C-terminus of SecM and the PTC, inducing conformational changes that allow for restart of translation. A similar mechanism of force propagation through multiple states is observed in the VemP stall-breaking pathway, but secondary structure in VemP allows for heterogeneity in the order of transitions through intermediate states. Results from both arrest peptides explain how residues that are tens of angstroms away from the catalytic center of the ribosome impact stalling efficiency by mediating the response to an applied force and shielding the amino acids responsible for maintaining the stalled state of the PTC.Significance StatementAs nascent proteins are synthesized by the ribosome, their interactions with the environment can create pulling forces on the nascent protein that can be transmitted to the ribosome’s catalytic center. These forces can affect the rate and even the outcome of translation. We use simulations to characterize the pathway of force transduction along arrest peptides and discover how secondary structure in the nascent protein and its interactions with the ribosome exit tunnel impede force propagation. This explains how amino acids in arrest peptides that are tens of angstroms away from the ribosome’s catalytic center contribute to stalling, and, more broadly, suggests how structural features in the nascent protein dictate the ribosome’s ability to functionally respond to its environment.

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Implications for the active form of human insulin based on the structural convergence of highly active hormone analogues

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0911785107 ◽

2010 ◽

Vol 107 (5) ◽

pp. 1966-1970 ◽

Cited By ~ 41

Author(s):

Jiří Jiráček ◽

Lenka Žáková ◽

Emília Antolíková ◽

Christopher J. Watson ◽

Johan P. Turkenburg ◽

...

Keyword(s):

Amino Acids ◽

Conformational Changes ◽

Rational Design ◽

Active Form ◽

Peptide Bond ◽

Insulin Analogues ◽

Exact Nature ◽

Glucose Levels ◽

Highly Active ◽

Monomeric Structure

Insulin is a key protein hormone that regulates blood glucose levels and, thus, has widespread impact on lipid and protein metabolism. Insulin action is manifested through binding of its monomeric form to the Insulin Receptor (IR). At present, however, our knowledge about the structural behavior of insulin is based upon inactive, multimeric, and storage-like states. The active monomeric structure, when in complex with the receptor, must be different as the residues crucial for the interactions are buried within the multimeric forms. Although the exact nature of the insulin’s induced-fit is unknown, there is strong evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Here, we present the design and analysis of highly active (200–500%) insulin analogues that are truncated at residue 26 of the B-chain (B26). They show a structural convergence in the form of a new β-turn at B24-B26. We propose that the key element in insulin’s transition, from an inactive to an active state, may be the formation of the β-turn at B24-B26 associated with a trans to cis isomerisation at the B25-B26 peptide bond. Here, this turn is achieved with N-methylated L-amino acids adjacent to the trans to cis switch at the B25-B26 peptide bond or by the insertion of certain D-amino acids at B26. The resultant conformational changes unmask previously buried amino acids that are implicated in IR binding and provide structural details for new approaches in rational design of ligands effective in combating diabetes.

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Structure and functions of 5S rRNA.

Acta Biochimica Polonica ◽

10.18388/abp.2001_5126 ◽

2001 ◽

Vol 48 (1) ◽

pp. 191-198 ◽

Cited By ~ 26

Author(s):

M Z Barciszewska ◽

M Szymański ◽

V A Erdmann ◽

J Barciszewski

Keyword(s):

Messenger Rna ◽

Protein Biosynthesis ◽

Large Subunit ◽

Genetic Material ◽

Ribosomal Subunit ◽

Peptide Bond ◽

Small Subunit ◽

5S Rrna ◽

23S Rrna ◽

Peptide Bond Formation

The ribosome is a macromolecular assembly that is responsible for protein biosynthesis in all organisms. It is composed of two-subunit, ribonucleoprotein particles that translate the genetic material into an encoded polypeptides. The small subunit is the site of codon-anticodon interaction between the messenger RNA (mRNA) and transfer RNA (tRNA) substrates, and the large subunit catalyses peptide bond formation. The peptidyltransferase activity is fulfilled by 23S rRNA, which means that ribosome is a ribozyme. 5S rRNA is a conserved component of the large ribosomal subunit that is thought to enhance protein synthesis by stabilizing ribosome structure. This paper shortly summarises new results obtained on the structure and function of 5S rRNA.

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The Kinetics of Inhibition of the Action of Thrombin by the Fibrinopeptides Formed during the Clotting of Fibrinogen

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655562 ◽

1966 ◽

Vol 16 (01/02) ◽

pp. 277-295 ◽

Cited By ~ 1

Author(s):

A Silver ◽

M Murray

Keyword(s):

Amino Acids ◽

Competitive Inhibition ◽

Amorphous Material ◽

Peptide Bond ◽

Initial Reaction ◽

Reaction Products ◽

Coagulation Mechanism ◽

Kinetics Of ◽

Kinetics Of Inhibition ◽

Burk Plot

SummaryVarious investigators have separated the coagulation products formed when fibrinogen is clotted with thrombin and identified fibrinopeptides A and B. Two other peaks are observed in the chromatogram of the products of coagulation, but these have mostly been dismissed by other workers. They have been identified by us as amino acids, smaller peptides and amorphous material (37). We have re-chromatographed these peaks and identified several amino acids. In a closed system of fibrinogen and thrombin, the only reaction products should be fibrin and peptide A and peptide B. This reasoning has come about because thrombin has been reported to be specific for the glycyl-arginyl peptide bond. It is suggested that thrombin also breaks other peptide linkages and the Peptide A and Peptide B are attacked by thrombin to yield proteolytic products. Thrombin is therefore probably not specific for the glycyl-arginyl bond but will react on other linkages as well.If the aforementioned is correct then the fibrinopeptides A and B would cause an inhibition with the coagulation mechanism itself. We have shown that an inhibition does occur. We suggest that there is an autoinhibition to the clotting mechanism that might be a control mechanism in the human body.The experiment was designed for coagulation to occur under controlled conditions of temperature and time. Purified reactants were used. We assembled an apparatus to record visually the speed of the initial reaction, the rate of the reaction, and the density of the final clot formed after a specific time.The figures we derived made available to us data whereby we could calculate and plot the information to show the mechanism and suggest that such an inhibition does exist and also further suggest that it might be competitive.In order to prove true competitive inhibition it is necessary to fulfill the criteria of the Lineweaver-Burk plot. This has been done. We have also satisfied other criteria of Dixon (29) and Bergman (31) that suggest true competitive inhibition.

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The Binding and Viscometric Studies of Ni+2, Co+2 and Mn+2 Ions with Protein by Spectrometric and pH Metric Techniques

Current Physical Chemistry ◽

10.2174/1877946809666190917144139 ◽

2019 ◽

Vol 9 (2) ◽

pp. 151-162

Author(s):

Shveta Acharya ◽

Arun Kumar Sharma

Keyword(s):

Metal Ions ◽

Metal Ion ◽

Protein Molecule ◽

Vital Role ◽

Sufficient Evidence ◽

Structural Requirement ◽

Nickel Ions ◽

Cobalt Ions ◽

Lower Temperature ◽

Specific Oxidation

Background: The metal ions play a vital role in a large number of widely differing biological processes. Some of these processes are quite specific in their metal ion requirements. In that only certain metal ions, in specific oxidation states, can full fill the necessary catalytic or structural requirement, while other processes are much less specific. Objective: In this paper we report the binding of Mn (II), Ni (II) and Co (II) with albumin are reported employing spectrophotometric and pH metric method. In order to distinguish between ionic and colloidal linking, the binding of metal by using pH metric and viscometric methods and the result are discussed in terms of electrovalent and coordinate bonding. Methods: The binding of Ni+2, Co+2 and Mn+2 ions have been studied with egg protein at different pH values and temperatures by the spectrometric technique. Results: The binding data were found to be pH and temperature dependent. The intrinsic association constants (k) and the number of binding sites (n) were calculated from Scatchard plots and found to be at the maximum at lower pH and at lower temperatures. Therefore, a lower temperature and lower pH offered more sites in the protein molecule for interaction with these metal ions. Statistical effects seem to be more significant at lower Ni+2, Co+2 and Mn+2 ions concentrations, while at higher concentrations electrostatic effects and heterogeneity of sites are more significant. Conclusion: The pH metric as well as viscometric data provided sufficient evidence about the linking of cobalt, nickel and manganese ions with the nitrogen groups of albumin. From the nature and height of curves in the three cases it may be concluded that nickel ions bound strongly while the cobalt ions bound weakly.

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Molecular docking studies of tea (Thea sinensis Linn.) polyphenols inhibition pattern with Rat P-glycoprotein

Physical Sciences Reviews ◽

10.1515/psr-2018-0165 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Babar Ali ◽

Qazi Mohammad Sajid Jamal ◽

Showkat R. Mir ◽

Saiba Shams ◽

Mohammad Amjad Kamal

Keyword(s):

Amino Acids ◽

Molecular Docking ◽

Binding Energy ◽

Oral Administration ◽

Docking Studies ◽

Vital Role ◽

Glycoprotein P ◽

High Affinity ◽

P Glycoprotein ◽

Inhibition Pattern

AbstractSince 3000 B.C., evergreen plant Thea sinensis (Theaceae) is used both as a social and medicinal beverage. Leaves of T. sinensis contain amino acids, vitamins, caffeine, polysaccharides and polyphenols. Most of the natural medicinal actions of tea are due to the availability and abundance of polyphenols mainly catechins. It has also been stated that some catechins were absorbed more rapidly than other compounds after the oral administration of tea and could increase the bio-enhancing activities of anticancer drugs by inhibiting P-glycoprotein (P-gp). The results of the molecular docking showed that polyphenols bind easily to the active P-gp site. All compounds exhibited fluctuating binding affinity ranged from −11.67 to −8.36 kcal/mol. Observed binding energy required for theaflavin to bind to P-gp was lowest (−11.67 kcal/mol). The obtained data that supports all the selected polyphenols inhibited P-gp and therefore may enhance the bioavailability of drugs. This study may play a vital role in finding hotspots in P-gp and eventually may be proved useful in designing compounds with high affinity and specificity to the protein.

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Epitope Mapping of Monoclonal Antibodies to Calreticulin Reveals That Charged Amino Acids Are Essential for Antibody Binding

Antibodies ◽

10.3390/antib10030031 ◽

2021 ◽

Vol 10 (3) ◽

pp. 31

Author(s):

Ann Christina Bergmann ◽

Cecilie Kyllesbech ◽

Rimantas Slibinskas ◽

Evaldas Ciplys ◽

Peter Højrup ◽

...

Keyword(s):

Amino Acids ◽

Monoclonal Antibodies ◽

Epitope Mapping ◽

Biological Function ◽

Specific Binding ◽

Enzyme Linked Immunosorbent Assay ◽

Potential Therapeutic Target ◽

Charged Amino Acids ◽

Chaperone Protein ◽

Terminal Amino

Calreticulin is a chaperone protein, which is associated with myeloproliferative diseases. In this study, we used resin-bound peptides to characterize two monoclonal antibodies (mAbs) directed to calreticulin, mAb FMC 75 and mAb 16, which both have significantly contributed to understanding the biological function of calreticulin. The antigenicity of the resin-bound peptides was determined by modified enzyme-linked immunosorbent assay. Specific binding was determined to an 8-mer epitope located in the N-terminal (amino acids 34–41) and to a 12-mer peptide located in the C-terminal (amino acids 362–373). Using truncated peptides, the epitopes were identified as TSRWIESK and DEEQRLKEEED for mAb FMC 75 and mAb 16, respectively, where, especially the charged amino acids, were found to have a central role for a stable binding. Further studies indicated that the epitope of mAb FMC 75 is assessable in the oligomeric structure of calreticulin, making this epitope a potential therapeutic target.

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The key amino acids of E protein involved in early flavivirus infection: viral entry

Virology Journal ◽

10.1186/s12985-021-01611-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Tao Hu ◽

Zhen Wu ◽

Shaoxiong Wu ◽

Shun Chen ◽

Anchun Cheng

Keyword(s):

Amino Acids ◽

Conformational Changes ◽

Viral Entry ◽

Envelope Protein ◽

Cell Attachment ◽

Envelope Proteins ◽

Infection Process ◽

Early Infection ◽

Protein Amino Acids ◽

Α Helix

AbstractFlaviviruses are enveloped viruses that infect multiple hosts. Envelope proteins are the outermost proteins in the structure of flaviviruses and mediate viral infection. Studies indicate that flaviviruses mainly use envelope proteins to bind to cell attachment receptors and endocytic receptors for the entry step. Here, we present current findings regarding key envelope protein amino acids that participate in the flavivirus early infection process. Among these sites, most are located in special positions of the protein structure, such as the α-helix in the stem region and the hinge region between domains I and II, motifs that potentially affect the interaction between different domains. Some of these sites are located in positions involved in conformational changes in envelope proteins. In summary, we summarize and discuss the key envelope protein residues that affect the entry process of flaviviruses, including the process of their discovery and the mechanisms that affect early infection.

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SSMBS: a web server to locate sequentially separated motifs in biological sequences

Journal of Applied Crystallography ◽

10.1107/s0021889809047050 ◽

2009 ◽

Vol 43 (1) ◽

pp. 203-205 ◽

Cited By ~ 1

Author(s):

Chetan Kumar ◽

K. Sekar

Keyword(s):

Amino Acids ◽

Web Server ◽

Nucleotide Sequences ◽

Regular Expressions ◽

Biological Sequences ◽

Sequence Motifs ◽

Specific Order ◽

The Web

The identification of sequence (amino acids or nucleotides) motifs in a particular order in biological sequences has proved to be of interest. This paper describes a computing server,SSMBS, which can locate and display the occurrences of user-defined biologically important sequence motifs (a maximum of five) present in a specific order in protein and nucleotide sequences. While the server can efficiently locate motifs specified using regular expressions, it can also find occurrences of long and complex motifs. The computation is carried out by an algorithm developed using the concepts of quantifiers in regular expressions. The web server is available to users around the clock at http://dicsoft1.physics.iisc.ernet.in/ssmbs/.

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Microglia extracellular vesicles: focus on molecular composition and biological function

Biochemical Society Transactions ◽

10.1042/bst20210202 ◽

2021 ◽

Vol 49 (4) ◽

pp. 1779-1790 ◽

Cited By ~ 1

Author(s):

Lorenzo Ceccarelli ◽

Chiara Giacomelli ◽

Laura Marchetti ◽

Claudia Martini

Keyword(s):

Extracellular Vesicles ◽

Molecular Mechanisms ◽

Biological Function ◽

Biological Effects ◽

Genetic Material ◽

Cell Communication ◽

Molecular Composition ◽

Cargo Proteins ◽

A Cell ◽

The Central Nervous System

Extracellular vesicles (EVs) are a heterogeneous family of cell-derived lipid bounded vesicles comprising exosomes and microvesicles. They are potentially produced by all types of cells and are used as a cell-to-cell communication method that allows protein, lipid, and genetic material exchange. Microglia cells produce a large number of EVs both in resting and activated conditions, in the latter case changing their production and related biological effects. Several actions of microglia in the central nervous system are ascribed to EVs, but the molecular mechanisms by which each effect occurs are still largely unknown. Conflicting functions have been ascribed to microglia-derived EVs starting from the neuronal support and ending with the propagation of inflammation and neurodegeneration, confirming the crucial role of these organelles in tuning brain homeostasis. Despite the increasing number of studies reported on microglia-EVs, there is also a lot of fragmentation in the knowledge on the mechanism at the basis of their production and modification of their cargo. In this review, a collection of literature data about the surface and cargo proteins and lipids as well as the miRNA content of EVs produced by microglial cells has been reported. A special highlight was given to the works in which the EV molecular composition is linked to a precise biological function.

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