Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins

Thomas J. Melia, Thomas Weber, James A. McNew, Lillian E. Fisher, Robert J. Johnston, Frank Parlati, Lara Mahal, Thomas H. Söllner, James E. Rothman

Research output: Contribution to journalArticle

Abstract

We utilize structurally targeted peptides to identify a "tc fusion switch" inherent to the coil domains of the neuronal t-SNARE that pairs with the cognate v-SNARE. The tc fusion switch is located in the membrane-proximal portion of the t-SNARE and controls the rate at which the helical bundle that forms the SNARE-pin can zip up to drive bilayer fusion. When the fusion switch is "off" (the intrinsic state of the t-SNARE), zippering of the helices from their membrane-distal ends is impeded and fusion is slow. When the tc fusion switch is "on," fusion is much faster. The tc fusion switch can be thrown by a peptide that corresponds to the membrane-proximal half of the cognate v-SNARE, and binds reversibly to the cognate region of the t-SNARE. This structures the coil in the membrane-proximal domain of the t-SNARE and accelerates fusion, implying that the intrinsically unstable coil in that region is a natural impediment to the completion of zippering, and thus, fusion. Proteins that stabilize or destabilize one or the other state of the tc fusion switch would exert fine temporal control over the rate of fusion after SNAREs have already partly zippered up.

Original languageEnglish (US)
Pages (from-to)929-940
Number of pages12
JournalJournal of Cell Biology
Volume158
Issue number5
DOIs
StatePublished - Sep 2 2002

Fingerprint

SNARE Proteins
Membrane Fusion
Membranes
Peptides

Keywords

  • Liposome
  • SNAP-25
  • Syntaxin
  • VAMP
  • Vesicle

ASJC Scopus subject areas

  • Cell Biology

Cite this

Melia, T. J., Weber, T., McNew, J. A., Fisher, L. E., Johnston, R. J., Parlati, F., ... Rothman, J. E. (2002). Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins. Journal of Cell Biology, 158(5), 929-940. https://doi.org/10.1083/jcb.200112081

Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins. / Melia, Thomas J.; Weber, Thomas; McNew, James A.; Fisher, Lillian E.; Johnston, Robert J.; Parlati, Frank; Mahal, Lara; Söllner, Thomas H.; Rothman, James E.

In: Journal of Cell Biology, Vol. 158, No. 5, 02.09.2002, p. 929-940.

Research output: Contribution to journalArticle

Melia, TJ, Weber, T, McNew, JA, Fisher, LE, Johnston, RJ, Parlati, F, Mahal, L, Söllner, TH & Rothman, JE 2002, 'Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins', Journal of Cell Biology, vol. 158, no. 5, pp. 929-940. https://doi.org/10.1083/jcb.200112081
Melia, Thomas J. ; Weber, Thomas ; McNew, James A. ; Fisher, Lillian E. ; Johnston, Robert J. ; Parlati, Frank ; Mahal, Lara ; Söllner, Thomas H. ; Rothman, James E. / Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins. In: Journal of Cell Biology. 2002 ; Vol. 158, No. 5. pp. 929-940.
@article{4da22c279f7d4d0eb6cea1fd46ffcc06,
title = "Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins",
abstract = "We utilize structurally targeted peptides to identify a {"}tc fusion switch{"} inherent to the coil domains of the neuronal t-SNARE that pairs with the cognate v-SNARE. The tc fusion switch is located in the membrane-proximal portion of the t-SNARE and controls the rate at which the helical bundle that forms the SNARE-pin can zip up to drive bilayer fusion. When the fusion switch is {"}off{"} (the intrinsic state of the t-SNARE), zippering of the helices from their membrane-distal ends is impeded and fusion is slow. When the tc fusion switch is {"}on,{"} fusion is much faster. The tc fusion switch can be thrown by a peptide that corresponds to the membrane-proximal half of the cognate v-SNARE, and binds reversibly to the cognate region of the t-SNARE. This structures the coil in the membrane-proximal domain of the t-SNARE and accelerates fusion, implying that the intrinsically unstable coil in that region is a natural impediment to the completion of zippering, and thus, fusion. Proteins that stabilize or destabilize one or the other state of the tc fusion switch would exert fine temporal control over the rate of fusion after SNAREs have already partly zippered up.",
keywords = "Liposome, SNAP-25, Syntaxin, VAMP, Vesicle",
author = "Melia, {Thomas J.} and Thomas Weber and McNew, {James A.} and Fisher, {Lillian E.} and Johnston, {Robert J.} and Frank Parlati and Lara Mahal and S{\"o}llner, {Thomas H.} and Rothman, {James E.}",
year = "2002",
month = "9",
day = "2",
doi = "10.1083/jcb.200112081",
language = "English (US)",
volume = "158",
pages = "929--940",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "5",

}

TY - JOUR

T1 - Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins

AU - Melia, Thomas J.

AU - Weber, Thomas

AU - McNew, James A.

AU - Fisher, Lillian E.

AU - Johnston, Robert J.

AU - Parlati, Frank

AU - Mahal, Lara

AU - Söllner, Thomas H.

AU - Rothman, James E.

PY - 2002/9/2

Y1 - 2002/9/2

N2 - We utilize structurally targeted peptides to identify a "tc fusion switch" inherent to the coil domains of the neuronal t-SNARE that pairs with the cognate v-SNARE. The tc fusion switch is located in the membrane-proximal portion of the t-SNARE and controls the rate at which the helical bundle that forms the SNARE-pin can zip up to drive bilayer fusion. When the fusion switch is "off" (the intrinsic state of the t-SNARE), zippering of the helices from their membrane-distal ends is impeded and fusion is slow. When the tc fusion switch is "on," fusion is much faster. The tc fusion switch can be thrown by a peptide that corresponds to the membrane-proximal half of the cognate v-SNARE, and binds reversibly to the cognate region of the t-SNARE. This structures the coil in the membrane-proximal domain of the t-SNARE and accelerates fusion, implying that the intrinsically unstable coil in that region is a natural impediment to the completion of zippering, and thus, fusion. Proteins that stabilize or destabilize one or the other state of the tc fusion switch would exert fine temporal control over the rate of fusion after SNAREs have already partly zippered up.

AB - We utilize structurally targeted peptides to identify a "tc fusion switch" inherent to the coil domains of the neuronal t-SNARE that pairs with the cognate v-SNARE. The tc fusion switch is located in the membrane-proximal portion of the t-SNARE and controls the rate at which the helical bundle that forms the SNARE-pin can zip up to drive bilayer fusion. When the fusion switch is "off" (the intrinsic state of the t-SNARE), zippering of the helices from their membrane-distal ends is impeded and fusion is slow. When the tc fusion switch is "on," fusion is much faster. The tc fusion switch can be thrown by a peptide that corresponds to the membrane-proximal half of the cognate v-SNARE, and binds reversibly to the cognate region of the t-SNARE. This structures the coil in the membrane-proximal domain of the t-SNARE and accelerates fusion, implying that the intrinsically unstable coil in that region is a natural impediment to the completion of zippering, and thus, fusion. Proteins that stabilize or destabilize one or the other state of the tc fusion switch would exert fine temporal control over the rate of fusion after SNAREs have already partly zippered up.

KW - Liposome

KW - SNAP-25

KW - Syntaxin

KW - VAMP

KW - Vesicle

UR - http://www.scopus.com/inward/record.url?scp=0037008962&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037008962&partnerID=8YFLogxK

U2 - 10.1083/jcb.200112081

DO - 10.1083/jcb.200112081

M3 - Article

VL - 158

SP - 929

EP - 940

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 5

ER -