Structure of the Yeast Polarity Protein Sro7 Reveals a SNARE Regulatory Mechanism

Journal Article · Mon Jul 09 04:00:00 EDT 2007 · Nature 446:567-571,2007

DOI:https://doi.org/10.1038/nature05635· OSTI ID:909805

Hattendorf, D A; Andreeva, A; Gangar, A; Brennwald, P J; Weis, W I

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 {beta}-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-{beta}-propeller fold similar to that of Sro7, but only tomosyn appears to retain the regulatory tail.

• Research Organization: Stanford Linear Accelerator Center (SLAC)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC02-76SF00515
• OSTI ID: 909805
• Report Number(s): SLAC-REPRINT-2007-089
• Journal Information: Nature 446:567-571,2007, Journal Name: Nature 446:567-571,2007 Vol. 446; ISSN NATUAS; ISSN 0028-0836
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
ACTIN
CRYSTAL STRUCTURE
LARVAE
MACHINERY
MEMBRANES
Other
OTHER
PLASMA
PROTEINS
YEASTS