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Conformational control through translocational regulation: a new view of secretory and membrane protein folding
Journal article   Peer reviewed

Conformational control through translocational regulation: a new view of secretory and membrane protein folding

Vishwanath R Lingappa, D. Thomas Rutkowski, Ramanujan S Hegde and Olaf S Andersen
BioEssays, Vol.24(8), pp.741-748
08/2002
DOI: 10.1002/bies.10130
PMID: 12210535

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Abstract

We suggest a new view of secretory and membrane protein folding that emphasizes the role of pathways of biogenesis in generating functional and conformational heterogeneity. In this view, heterogeneity results from action of accessory factors either directly binding specific sequences of the nascent chain, or indirectly, changing the environment in which a particular domain is synthesized. Entrained by signaling pathways, these variables create a combinatorial set of necessary-but-not-sufficient conditions that enhance synthesis and folding of particular alternate, functional, conformational forms. We therefore propose that protein conformation is productively regulated by the cell during translocation across the endoplasmic reticulum (ER), a concept that may account for currently poorly understood aspects of physiological function, natural selection, and disease pathogenesis.

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