Is peptide bond cis/trans isomerization a key stage in the chemo‐mechanical cycle of motor proteins?

Abstract

Motor proteins such as myosin and kinesin are responsible for actively directed movement in vivo. The physicochemical mechanism underlying their function is still obscure. A novel and unifying model concerning the motors driving mechanism is suggested here. This model resides within the framework of the well-studied "swinging lever-arm" hypothesis, stating that cis/trans peptide bond isomerization (CTI) is a key stage in the chemo-mechanical coupling within actomyosin--the complex of the motor (myosin) and its specific track (actin). CTI is suggested to propel myosin's lever-arm swing. The model addresses on the submolecular level a broad spectrum of actomyosin's functional characteristics, such as kinetics, energetics, force exertion, stepping, and directionality. The model may be tested first with relative ease in kinesin--a smaller motor that could be specifically modified with unnatural amino acids using bacterial expression. Suggested modifications may be used for labeling and functional decoupling.

Conformational Dynamics of Minimal Elastin‐Like Polypeptides: The Role of Proline Revealed by Molecular Dynamics and Nuclear Magnetic Resonance

“…[18,19] Interestingly, in a recent paper, it was proposed that cis-trans peptide-bond isomerization is involved in the chemical-to-mechanical energy transduction in myosin. [20] Along the same lines, it has also been proposed that prolyl cis-trans isomerization in proteins can cause local structural changes which facilitate an elongation or a contraction of the protein's backbone. [21] The aim of this work is to continue the theoretical studies carried out previously on the minimal ELP model GVGA C H T U N G T R E N N U N G (VPGVG) in refs.…”

A model for the role of isomerization in nascent peptide movement through the ribosomal tunnel

“…The cis‐trans peptide bond isomerization was suggested to be a key step in the chemomechanical coupling of biological motors (16), and it is used by rhodopsin molecular machines, involved in vision processes, to convert photons into electrical signals (17). Potential energy of 0.5‐4 kcal/mol (16), stored in the unfavorable cis conformer of the bond, is released during the interconversion into the more stable trans state and can be utilized for the specific action of the machine. Uncatalyzed cis to trans isomerization rates are of ~10 –2 s –1 for an Xaa‐Pro bond (Xaa being any amino acid) and ~2 orders of magnitude faster for the other peptide bonds (18).…”

Properties of the Amide Bond Involving Proline 4,5‐methanologues: an Experimental and Theoretical Study

“…Proline occupies a special place within the series of natural amino acids and it continues to garner much attention from the scientific community. In addition to being the only secondary amine among the natural amino acids, the propensity of proline to adopt the cis ‐conformation of its peptide bond with a much higher frequency compared to all other amino acids (around 5% versus less than 0.1%), makes it a key amino acid to study various aspects of protein structure and function, playing critical roles in a wide variety of biological processes …”