Sequential triage of transmembrane segments by Sec61α during biogenesis of a native multispanning membrane protein

Heather Sadlish, David Pitonzo, Arthur E. Johnson, William Skach

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

During polytopic protein biogenesis, the Sec61 translocon must rapidly orient and integrate multiple transmembrane segments (TMs) into the endoplasmic reticulum membrane. To understand this process, we examined interactions between Sec61α and all six TMs of the aquaporin-4 (AQP4) water channel at defined stages of synthesis using incorporated photo-cross-linking probes. Each TM interacted with and moved through the translocon in a highly ordered and sequential fashion. Strong asymmetric Sec61α cross-linking was observed for only one helix at a time, suggesting the presence of a single primary binding site. However, up to four TMs simultaneously contacted Sec61α from different molecular environments. Thus, AQP4 integration by Sec61α involves sequential triage of TMs from their initial portal of entry into multiple secondary sites within the translocon. This mechanism provides a means to facilitate early folding events before release into the lipid bilayer.

Original languageEnglish (US)
Pages (from-to)870-878
Number of pages9
JournalNature Structural and Molecular Biology
Volume12
Issue number10
DOIs
StatePublished - Oct 2005

Fingerprint

Aquaporin 4
Triage
Membrane Proteins
Aquaporins
Lipid Bilayers
Endoplasmic Reticulum
Binding Sites
Membranes
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Sequential triage of transmembrane segments by Sec61α during biogenesis of a native multispanning membrane protein. / Sadlish, Heather; Pitonzo, David; Johnson, Arthur E.; Skach, William.

In: Nature Structural and Molecular Biology, Vol. 12, No. 10, 10.2005, p. 870-878.

Research output: Contribution to journalArticle

Sadlish, Heather ; Pitonzo, David ; Johnson, Arthur E. ; Skach, William. / Sequential triage of transmembrane segments by Sec61α during biogenesis of a native multispanning membrane protein. In: Nature Structural and Molecular Biology. 2005 ; Vol. 12, No. 10. pp. 870-878.
@article{7604ee389392489380c9c6e71a02cac4,
title = "Sequential triage of transmembrane segments by Sec61α during biogenesis of a native multispanning membrane protein",
abstract = "During polytopic protein biogenesis, the Sec61 translocon must rapidly orient and integrate multiple transmembrane segments (TMs) into the endoplasmic reticulum membrane. To understand this process, we examined interactions between Sec61α and all six TMs of the aquaporin-4 (AQP4) water channel at defined stages of synthesis using incorporated photo-cross-linking probes. Each TM interacted with and moved through the translocon in a highly ordered and sequential fashion. Strong asymmetric Sec61α cross-linking was observed for only one helix at a time, suggesting the presence of a single primary binding site. However, up to four TMs simultaneously contacted Sec61α from different molecular environments. Thus, AQP4 integration by Sec61α involves sequential triage of TMs from their initial portal of entry into multiple secondary sites within the translocon. This mechanism provides a means to facilitate early folding events before release into the lipid bilayer.",
author = "Heather Sadlish and David Pitonzo and Johnson, {Arthur E.} and William Skach",
year = "2005",
month = "10",
doi = "10.1038/nsmb994",
language = "English (US)",
volume = "12",
pages = "870--878",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Sequential triage of transmembrane segments by Sec61α during biogenesis of a native multispanning membrane protein

AU - Sadlish, Heather

AU - Pitonzo, David

AU - Johnson, Arthur E.

AU - Skach, William

PY - 2005/10

Y1 - 2005/10

N2 - During polytopic protein biogenesis, the Sec61 translocon must rapidly orient and integrate multiple transmembrane segments (TMs) into the endoplasmic reticulum membrane. To understand this process, we examined interactions between Sec61α and all six TMs of the aquaporin-4 (AQP4) water channel at defined stages of synthesis using incorporated photo-cross-linking probes. Each TM interacted with and moved through the translocon in a highly ordered and sequential fashion. Strong asymmetric Sec61α cross-linking was observed for only one helix at a time, suggesting the presence of a single primary binding site. However, up to four TMs simultaneously contacted Sec61α from different molecular environments. Thus, AQP4 integration by Sec61α involves sequential triage of TMs from their initial portal of entry into multiple secondary sites within the translocon. This mechanism provides a means to facilitate early folding events before release into the lipid bilayer.

AB - During polytopic protein biogenesis, the Sec61 translocon must rapidly orient and integrate multiple transmembrane segments (TMs) into the endoplasmic reticulum membrane. To understand this process, we examined interactions between Sec61α and all six TMs of the aquaporin-4 (AQP4) water channel at defined stages of synthesis using incorporated photo-cross-linking probes. Each TM interacted with and moved through the translocon in a highly ordered and sequential fashion. Strong asymmetric Sec61α cross-linking was observed for only one helix at a time, suggesting the presence of a single primary binding site. However, up to four TMs simultaneously contacted Sec61α from different molecular environments. Thus, AQP4 integration by Sec61α involves sequential triage of TMs from their initial portal of entry into multiple secondary sites within the translocon. This mechanism provides a means to facilitate early folding events before release into the lipid bilayer.

UR - http://www.scopus.com/inward/record.url?scp=27144549973&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27144549973&partnerID=8YFLogxK

U2 - 10.1038/nsmb994

DO - 10.1038/nsmb994

M3 - Article

C2 - 16186821

AN - SCOPUS:27144549973

VL - 12

SP - 870

EP - 878

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 10

ER -