Ribosomal tunnel and translation regulation

Abstract

This review describes the results of recent studies of the ribosomal tunnel (RT), the major function of which is to allow the smooth passage of nascent polypeptides with different sequences from the peptidyl transferase center of the ribosome to the tunnel exit, where the folding of protein molecules begins. The features of structural organization of RT and their role in modulation and stabilization of the nascent chain conformation are discussed. Structural features of macrolide binding sites as well as application of macrolide antibiotics and their derivatives as tools to investigate ligand-tunnel wall interactions are also considered. Several examples of strong and specific interactions of regulatory polypeptides with nucleotide and amino acid residues of RT that lead to ribosome stalling and translational arrest are described in detail. The role of these events in regulation of expression of certain genes is discussed on the basis of recent high-resolution structural studies of nascent chains in the RT.

Direct imaging electron microscopy (EM) methods in modern structural biology: Overview and comparison with X‐ray crystallography and single‐particle cryo‐EM reconstruction in the studies of large macromolecules

“…() analysed localisation of the nascent peptide and obtained results different from the results presented by Lake et al., contradicting the concept of an intra‐ribosomal tunnel. This discrepancy was not resolved at the time, but the concept of a large intra‐subunit tunnel concept was later supported by the results of a number of studies utilising analytical structural methods, including single‐particle cryo‐EM reconstruction and X‐ray crystallography (Bogdanov et al., , for review). These studies characterised the tunnel structure in detail (Figure ).…”

Use of a Novel 5′‐Regioselective Phosphitylating Reagent for One‐Pot Synthesis of Nucleoside 5′‐Triphosphates from Unprotected Nucleosides

“…Nucleoside 5′‐triphosphates (NTPs and dNTPs) play key roles in biochemistry, molecular biology, and medicine (Eckstein, ; Bogdanov et al, ). They are the essential building blocks for synthesis of nucleic acids, both in vivo and in vitro, and depend on template, primer, and polymerases to perform their functions.…”

Thermodynamics of Helix–Coil Transitions of Polyalanine in Open Carbon Nanotubes

“…Confinement of biopolymers and synthetic materials in nanopores play an important role in DNA sequencing, drug delivery, biotechnology applications, folding, , degradation of proteins, and in the design of biosensors. , The structural transitions that occur when water-soluble synthetic polymers are encapsulated in nanotubes (NT) are important in the design of nanomaterials for use in membrane separation and energy related applications. Another example of considerable interest in biology is the influence of the cylindrical ribosome tunnel through which the newly synthesized protein must pass and how it facilitates structure formation. − The tunnel diameter varies between 10 and 20 Å with an average of approximately 15 Å . A number of experiments have shown there are zones within the tunnel that are conducive to compaction and α-helix formation. − , Theoretical studies indicate conformational restrictions of the coiled state in a confined system make it entropically more unfavorable than the α-helix, thus favoring the formation of the helical state. − We investigate this here and study the thermodynamics of coil–helix transition of polyalanine encapsulated in nanotubes open to water reservoirs.…”

“…9−13 The tunnel diameter varies between 10 and 20 Å with an average of approximately 15 Å. 14 A number of experiments have shown there are zones within the tunnel that are conducive to compaction and α-helix formation. [9][10][11][12][13]15 Theoretical studies indicate conformational restrictions of the coiled state in a confined system make it entropically more unfavorable than the α-helix, thus favoring the formation of the helical state.…”