Abstract
Soluble N-ethylmaleimide sensitive factor-attachment protein receptors (SNAREs) and Sec1p/Munc18 homologs (SM proteins) play key roles in intracellular membrane fusion. The SNAREs form tight four-helix bundles (core complexes) that bring the membranes together, but it is unclear how this activity is coupled to SM protein function. Studies of the yeast trans-Golgi network (TGN)/endosomal SNARE complex, which includes the syntaxin-like SNARE Tlg2p, have suggested that its assembly requires activation by binding of the SM protein Vps45p to the cytoplasmic region of Tlg2p folded into a closed conformation. Nuclear magnetic resonance and biochemical experiments now show that Tlg2p and Pep12p, a late-endosomal syntaxin that interacts functionally but not directly with Vps45p, have a domain structure characteristic of syntaxins but do not adopt a closed conformation. Tlg2p binds tightly to Vps45p via a short N-terminal peptide motif that is absent in Pep12p. The Tlg2p/Vps45p binding mode is shared by the mammalian syntaxin 16, confirming that it is a Tlg2p homolog, and resembles the mode of interaction between the SM protein Sly1p and the syntaxins Ufe1p and Sed5p. Thus, this mechanism represents the most widespread mode of coupling between syntaxins and SM proteins.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3620-3631 |
| Number of pages | 12 |
| Journal | EMBO Journal |
| Volume | 21 |
| Issue number | 14 |
| DOIs | |
| State | Published - Jul 15 2002 |
Fingerprint
Keywords
- SM proteins
- SNAREs
- Syntaxins
- Tlg2p
- Vps45p
ASJC Scopus subject areas
- Genetics
- Cell Biology
Cite this
How Tlg2p/syntaxin 16 'snares' Vps45. / Dulubova, Irina; Yamaguchi, Tomohiro; Gao, Yan; Min, Sang Won; Huryeva, Iryna; Südhof, Thomas C.; Rizo-Rey, Jose.
In: EMBO Journal, Vol. 21, No. 14, 15.07.2002, p. 3620-3631.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - How Tlg2p/syntaxin 16 'snares' Vps45
AU - Dulubova, Irina
AU - Yamaguchi, Tomohiro
AU - Gao, Yan
AU - Min, Sang Won
AU - Huryeva, Iryna
AU - Südhof, Thomas C.
AU - Rizo-Rey, Jose
PY - 2002/7/15
Y1 - 2002/7/15
N2 - Soluble N-ethylmaleimide sensitive factor-attachment protein receptors (SNAREs) and Sec1p/Munc18 homologs (SM proteins) play key roles in intracellular membrane fusion. The SNAREs form tight four-helix bundles (core complexes) that bring the membranes together, but it is unclear how this activity is coupled to SM protein function. Studies of the yeast trans-Golgi network (TGN)/endosomal SNARE complex, which includes the syntaxin-like SNARE Tlg2p, have suggested that its assembly requires activation by binding of the SM protein Vps45p to the cytoplasmic region of Tlg2p folded into a closed conformation. Nuclear magnetic resonance and biochemical experiments now show that Tlg2p and Pep12p, a late-endosomal syntaxin that interacts functionally but not directly with Vps45p, have a domain structure characteristic of syntaxins but do not adopt a closed conformation. Tlg2p binds tightly to Vps45p via a short N-terminal peptide motif that is absent in Pep12p. The Tlg2p/Vps45p binding mode is shared by the mammalian syntaxin 16, confirming that it is a Tlg2p homolog, and resembles the mode of interaction between the SM protein Sly1p and the syntaxins Ufe1p and Sed5p. Thus, this mechanism represents the most widespread mode of coupling between syntaxins and SM proteins.
AB - Soluble N-ethylmaleimide sensitive factor-attachment protein receptors (SNAREs) and Sec1p/Munc18 homologs (SM proteins) play key roles in intracellular membrane fusion. The SNAREs form tight four-helix bundles (core complexes) that bring the membranes together, but it is unclear how this activity is coupled to SM protein function. Studies of the yeast trans-Golgi network (TGN)/endosomal SNARE complex, which includes the syntaxin-like SNARE Tlg2p, have suggested that its assembly requires activation by binding of the SM protein Vps45p to the cytoplasmic region of Tlg2p folded into a closed conformation. Nuclear magnetic resonance and biochemical experiments now show that Tlg2p and Pep12p, a late-endosomal syntaxin that interacts functionally but not directly with Vps45p, have a domain structure characteristic of syntaxins but do not adopt a closed conformation. Tlg2p binds tightly to Vps45p via a short N-terminal peptide motif that is absent in Pep12p. The Tlg2p/Vps45p binding mode is shared by the mammalian syntaxin 16, confirming that it is a Tlg2p homolog, and resembles the mode of interaction between the SM protein Sly1p and the syntaxins Ufe1p and Sed5p. Thus, this mechanism represents the most widespread mode of coupling between syntaxins and SM proteins.
KW - SM proteins
KW - SNAREs
KW - Syntaxins
KW - Tlg2p
KW - Vps45p
UR - http://www.scopus.com/inward/record.url?scp=0037099492&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037099492&partnerID=8YFLogxK
U2 - 10.1093/emboj/cdf381
DO - 10.1093/emboj/cdf381
M3 - Article
C2 - 12110575
AN - SCOPUS:0037099492
VL - 21
SP - 3620
EP - 3631
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 14
ER -