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Conformational control through translocational regulation: a new view of secretory and membrane protein folding
Author(s) -
Lingappa Vishwanath R.,
Rutkowski D. Thomas,
Hegde Ramanujan S.,
Andersen Olaf S.
Publication year - 2002
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.10130
Subject(s) - endoplasmic reticulum , biogenesis , folding (dsp implementation) , protein folding , function (biology) , biology , translocon , microbiology and biotechnology , secretory protein , computational biology , membrane protein , chemistry , biochemistry , membrane , gene , engineering , electrical engineering
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. BioEssays 24:741–748, 2002. © 2002 Wiley Periodicals, Inc.