Cellular mechanisms of membrane protein folding.
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.
Skach
William R
WR
William R Skach is in the Department of Biochemistry & Molecular Biology, Oregon Health & Sciences University, Portland, Oregon, USA. skachw@ohsu.edu
D000818:Animals; D051398:Aquaporin 1 / Q000737:chemistry / Q000378:metabolism; D051401:Aquaporin 4 / Q000737:chemistry / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D011487:Protein Conformation; D017510:Protein Folding; D021381:Protein Transport; D012270:Ribosomes / Q000378:metabolism; D000069816:SEC Translocation Channels
D051401:Aquaporin 4; D008565:Membrane Proteins; D018832:Molecular Chaperones; D000069816:SEC Translocation Channels; D051398:Aquaporin 1