Pushing, pulling and trapping – Modes of motor protein supported protein translocation

Abstract 

Protein translocation across the cellular membranes is an ubiquitous and crucial activity of cells. This process is mediated by translocases that consist of a protein conducting channel and an associated motor protein. Motor proteins interact with protein substrates and utilize the free energy of ATP binding and hydrolysis for protein unfolding, translocation and unbinding. Since motor proteins are found either at the cis- or trans-side of the membrane, different mechanisms for translocation have been proposed. In the Power stroke model, cis-acting motors are thought to push, while trans-motors pull on the substrate protein during translocation. In the Brownian ratchet model, translocation occurs by diffusion of the unfolded polypeptide through the translocation pore while directionality is achieved by trapping and refolding. Recent insights in the structure and function of the molecular motors suggest that different mechanisms can be employed simultaneously.

Abbreviations: CTD, small C-terminal zinc-binding domain, ER, endoplasmic reticulum, JDP, J-domain protein, NBD, nucleotide binding domain, NEF, nucleotide exchange factor, PAM, presequence translocase-associated motor, PBD, preprotein binding domain, PCC, protein conducting channel, PMF, proton motive force, ΔpH, transmembrane pH gradient, Δψ, transmembrane electrical potential

Keywords: Translocation, Molecular motor, Secretory protein, SecA, BiP, Hsp70