Cellular mechanisms of membrane protein folding

William Skach

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

The membrane protein-folding problem can be articulated by two central questions. How is protein topology established by selective peptide transport to opposite sides of the cellular membrane? And how are transmembrane segments inserted, integrated and folded within the lipid bilayer? In eukaryotes, this process usually takes place in the endoplasmic reticulum, coincident with protein synthesis, and is facilitated by the translating ribosome and the Sec61 translocon complex (RTC). At its core, the RTC forms a dynamic pathway through which the elongating nascent polypeptide moves as it is delivered into the cytosolic, lumenal and lipid compartments. This Perspective will focus on emerging evidence that the RTC functions as a protein-folding machine that restricts conformational space by establishing transmembrane topology and yet provides a permissive environment that enables nascent transmembrane domains to efficiently progress down their folding energy landscape.

Original languageEnglish (US)
Pages (from-to)606-612
Number of pages7
JournalNature Structural and Molecular Biology
Volume16
Issue number6
DOIs
StatePublished - Jun 2009

Fingerprint

Protein Folding
Ribosomes
Membrane Proteins
Peptides
Lipid Bilayers
Eukaryota
Endoplasmic Reticulum
Proteins
Lipids
Membranes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Cellular mechanisms of membrane protein folding. / Skach, William.

In: Nature Structural and Molecular Biology, Vol. 16, No. 6, 06.2009, p. 606-612.

Research output: Contribution to journalArticle

Skach, William. / Cellular mechanisms of membrane protein folding. In: Nature Structural and Molecular Biology. 2009 ; Vol. 16, No. 6. pp. 606-612.
@article{46405823350d4d65a22bbee773df839d,
title = "Cellular mechanisms of membrane protein folding",
abstract = "The membrane protein-folding problem can be articulated by two central questions. How is protein topology established by selective peptide transport to opposite sides of the cellular membrane? And how are transmembrane segments inserted, integrated and folded within the lipid bilayer? In eukaryotes, this process usually takes place in the endoplasmic reticulum, coincident with protein synthesis, and is facilitated by the translating ribosome and the Sec61 translocon complex (RTC). At its core, the RTC forms a dynamic pathway through which the elongating nascent polypeptide moves as it is delivered into the cytosolic, lumenal and lipid compartments. This Perspective will focus on emerging evidence that the RTC functions as a protein-folding machine that restricts conformational space by establishing transmembrane topology and yet provides a permissive environment that enables nascent transmembrane domains to efficiently progress down their folding energy landscape.",
author = "William Skach",
year = "2009",
month = "6",
doi = "10.1038/nsmb.1600",
language = "English (US)",
volume = "16",
pages = "606--612",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Cellular mechanisms of membrane protein folding

AU - Skach, William

PY - 2009/6

Y1 - 2009/6

N2 - The membrane protein-folding problem can be articulated by two central questions. How is protein topology established by selective peptide transport to opposite sides of the cellular membrane? And how are transmembrane segments inserted, integrated and folded within the lipid bilayer? In eukaryotes, this process usually takes place in the endoplasmic reticulum, coincident with protein synthesis, and is facilitated by the translating ribosome and the Sec61 translocon complex (RTC). At its core, the RTC forms a dynamic pathway through which the elongating nascent polypeptide moves as it is delivered into the cytosolic, lumenal and lipid compartments. This Perspective will focus on emerging evidence that the RTC functions as a protein-folding machine that restricts conformational space by establishing transmembrane topology and yet provides a permissive environment that enables nascent transmembrane domains to efficiently progress down their folding energy landscape.

AB - The membrane protein-folding problem can be articulated by two central questions. How is protein topology established by selective peptide transport to opposite sides of the cellular membrane? And how are transmembrane segments inserted, integrated and folded within the lipid bilayer? In eukaryotes, this process usually takes place in the endoplasmic reticulum, coincident with protein synthesis, and is facilitated by the translating ribosome and the Sec61 translocon complex (RTC). At its core, the RTC forms a dynamic pathway through which the elongating nascent polypeptide moves as it is delivered into the cytosolic, lumenal and lipid compartments. This Perspective will focus on emerging evidence that the RTC functions as a protein-folding machine that restricts conformational space by establishing transmembrane topology and yet provides a permissive environment that enables nascent transmembrane domains to efficiently progress down their folding energy landscape.

UR - http://www.scopus.com/inward/record.url?scp=66849131417&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66849131417&partnerID=8YFLogxK

U2 - 10.1038/nsmb.1600

DO - 10.1038/nsmb.1600

M3 - Article

C2 - 19491932

AN - SCOPUS:66849131417

VL - 16

SP - 606

EP - 612

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 6

ER -