The DOI matches its Crossref record; 149 of the 149 references it cites were found in a registry or an index.
Mechanisms of Integral Membrane Protein Insertion and Folding
Open accessAbstract
The biogenesis, folding, and structure of α-helical membrane proteins (MPs) are important to understand because they underlie virtually all physiological processes in cells including key metabolic pathways, such as the respiratory chain and the photosystems, and the transport of solutes and signals across membranes. Nearly all MPs require translocons—often referred to as protein-conducting channels—for proper insertion into their target membrane. Remarkable progress toward understanding the structure and functioning of translocons has been made during the past decade. Here we review and assess this progress critically. All available evidence indicates that MPs are equilibrium structures that achieve their final structural states by folding along thermodynamically controlled pathways. The main challenge for cells is the targeting and membrane insertion of highly hydrophobic amino acid sequences. Targeting and insertion are managed in cells principally by interactions between ribosomes and membrane-embedded translocons. Our review examines the biophysical and biological boundaries of membrane protein insertion and the folding of polytopic membrane proteins in vivo. A theme of the review is the under-appreciated role of basic thermodynamic principles in MP folding and assembly. Thermodynamics not only dictates the final folded structure, it is the driving force for the evolution of the ribosome-translocon system of assembly. We conclude the review with a perspective suggesting a new view of translocon-guided MP insertion.
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Cited by
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Documentation of an Imperative To Improve Methods for Predicting Membrane Protein Stability
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Partially inserted nascent chain unzips the lateral gate of the Sec translocon.
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SLC6 Transporter Folding Diseases and Pharmacochaperoning
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Insertion and folding pathways of single membrane proteins guided by translocases and insertases
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Metadata
- Authors
- Cymer, F., von Heijne, G., & White, S. H.
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 427
- Issue
- 5
- Pages
- 999-1022
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W1969549030
- Cited by
- 360
- References
- 149
- FWCI
- 12.90
- Type
- journal article
- Language
- en
- Open access
- green
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