Structure of the yeast polarity protein Sro7 reveals a SNARE regulatory mechanism.
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.
Hattendorf
Douglas A
DA
Department of Structural Biology, Stanford University School of Medicine, 299 Campus Drive West, Stanford, California 94305-5126, USA.
Andreeva
Anna
A
Gangar
Akanksha
A
Brennwald
Patrick J
PJ
Weis
William I
WI
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D005089:Exocytosis; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D050767:Qc-SNARE Proteins / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D050767:Qc-SNARE Proteins; C090117:SEC9 protein, S cerevisiae; C116430:SRO7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins