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, 182 (2), 225-32

The Concept of Translocational Regulation


The Concept of Translocational Regulation

Ramanujan S Hegde et al. J Cell Biol.


Biological processes are regulated to provide cells with exquisite adaptability to changing environmental conditions and cellular demands. The mechanisms regulating secretory and membrane protein translocation into the endoplasmic reticulum (ER) are unknown. A conceptual framework for translocational regulation is proposed based on our current mechanistic understanding of ER protein translocation and general principles of regulatory control.


Figure 1.
Figure 1.
The essential steps in cotranslational translocation. (A) SRP-dependent targeting of a signal- or TMD-containing nascent chain to the Sec61 translocon. (B) Modes of interaction between signals and TMDs with the Sec61 translocon. (C) The diversity of signal sequences: the overall length and net charge of the n domain (green) are listed for a set of typical signals. The hydrophobic core of each signal sequence is indicated in red underlined text.
Figure 2.
Figure 2.
A dynamic signal–Sec61 interaction. After targeting to the Sec61 complex (top), the signal sequence is proposed to interact weakly and dynamically with the putative signal binding site on Sec61. The looped (right) and nonlooped (left) configurations are more interconvertible at shorter nascent chain lengths than at longer lengths.
Figure 3.
Figure 3.
Potential mechanisms of translocational regulation. (A) Selective stabilization of the looped conformation by accessory factors (light blue; right). (B) Trapping of transiently sampled conformations by nascent chain binding proteins (such as a chaperone; pink). (C) Alteration of Sec61 functionality by an accessory factor (green) or by a modification (yellow star) that changes its signal recognition properties.

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