Abstract
Polarized exocytosis requires coordination between the actin cytoskeleton and the exocytic machinery responsible for fusion of secretory vesicles at specific sites on the plasma membrane. Fusion requires formation of a complex between a vesicle-bound R-SNARE and plasma membrane Qa, Qb and Qc SNARE proteins. Proteins in the lethal giant larvae protein family, including lethal giant larvae and tomosyn in metazoans and Sro7 in yeast, interact with Q-SNAREs and are emerging as key regulators of polarized exocytosis. The crystal structure of Sro7 reveals two seven-bladed WD40 β-propellers followed by a 60-residue-long 'tail', which is bound to the surface of the amino-terminal propeller. Deletion of the Sro7 tail enables binding to the Qbc SNARE region of Sec9 and this interaction inhibits SNARE complex assembly. The N-terminal domain of Sec9 provides a second, high-affinity Sro7 interaction that is unaffected by the tail. The results suggest that Sro7 acts as an allosteric regulator of exocytosis through interactions with factors that control the tail. Sequence alignments indicate that lethal giant larvae and tomosyn have a two-β-propeller fold similar to that of Sro7, but only tomosyn appears to retain the regulatory tail.
| Original language | English |
|---|---|
| Pages (from-to) | 567-571 |
| Number of pages | 5 |
| Journal | Nature |
| Volume | 446 |
| Issue number | 7135 |
| DOIs | |
| Publication status | Published - Mar 29 2007 |
| Externally published | Yes |
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Cite this
Structure of the yeast polarity protein Sro7 reveals a SNARE regulatory mechanism. / Hattendorf, Douglas A.; Andreeva, Anna; Gangar, Akanksha; Brennwald, Patrick J.; Weis, William I.
In: Nature, Vol. 446, No. 7135, 29.03.2007, p. 567-571.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structure of the yeast polarity protein Sro7 reveals a SNARE regulatory mechanism
AU - Hattendorf, Douglas A.
AU - Andreeva, Anna
AU - Gangar, Akanksha
AU - Brennwald, Patrick J.
AU - Weis, William I.
PY - 2007/3/29
Y1 - 2007/3/29
N2 - Polarized exocytosis requires coordination between the actin cytoskeleton and the exocytic machinery responsible for fusion of secretory vesicles at specific sites on the plasma membrane. Fusion requires formation of a complex between a vesicle-bound R-SNARE and plasma membrane Qa, Qb and Qc SNARE proteins. Proteins in the lethal giant larvae protein family, including lethal giant larvae and tomosyn in metazoans and Sro7 in yeast, interact with Q-SNAREs and are emerging as key regulators of polarized exocytosis. The crystal structure of Sro7 reveals two seven-bladed WD40 β-propellers followed by a 60-residue-long 'tail', which is bound to the surface of the amino-terminal propeller. Deletion of the Sro7 tail enables binding to the Qbc SNARE region of Sec9 and this interaction inhibits SNARE complex assembly. The N-terminal domain of Sec9 provides a second, high-affinity Sro7 interaction that is unaffected by the tail. The results suggest that Sro7 acts as an allosteric regulator of exocytosis through interactions with factors that control the tail. Sequence alignments indicate that lethal giant larvae and tomosyn have a two-β-propeller fold similar to that of Sro7, but only tomosyn appears to retain the regulatory tail.
AB - Polarized exocytosis requires coordination between the actin cytoskeleton and the exocytic machinery responsible for fusion of secretory vesicles at specific sites on the plasma membrane. Fusion requires formation of a complex between a vesicle-bound R-SNARE and plasma membrane Qa, Qb and Qc SNARE proteins. Proteins in the lethal giant larvae protein family, including lethal giant larvae and tomosyn in metazoans and Sro7 in yeast, interact with Q-SNAREs and are emerging as key regulators of polarized exocytosis. The crystal structure of Sro7 reveals two seven-bladed WD40 β-propellers followed by a 60-residue-long 'tail', which is bound to the surface of the amino-terminal propeller. Deletion of the Sro7 tail enables binding to the Qbc SNARE region of Sec9 and this interaction inhibits SNARE complex assembly. The N-terminal domain of Sec9 provides a second, high-affinity Sro7 interaction that is unaffected by the tail. The results suggest that Sro7 acts as an allosteric regulator of exocytosis through interactions with factors that control the tail. Sequence alignments indicate that lethal giant larvae and tomosyn have a two-β-propeller fold similar to that of Sro7, but only tomosyn appears to retain the regulatory tail.
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UR - http://www.scopus.com/inward/citedby.url?scp=34047100822&partnerID=8YFLogxK
U2 - 10.1038/nature05635
DO - 10.1038/nature05635
M3 - Article
C2 - 17392788
AN - SCOPUS:34047100822
VL - 446
SP - 567
EP - 571
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7135
ER -