Allosteric regulation of exocyst: Discrete activation of tethering by two spatial signals.
The exocyst imparts spatial control during exocytic vesicle tethering through its interactions with proteins and lipids on the vesicle and the plasma membrane. One such interaction is with the vesicle tether Sro7, although the outcome of this interaction is poorly understood. Here, we describe how Sro7 binding to the Exo84 ... subunit results in activation of the exocyst complex which leads to an increase in avidity for the Rab GTPase Sec4 and an increase in exocyst-mediated vesicle tethering. Gain-of-function (GOF) mutations in Exo84 that mimic Sro7 activation replicate these biochemical changes and result in allosteric changes within the complex. Direct comparison of GOF mutants which mimic Sro7- and Rho/Cdc42-activation of the exocyst reveals distinct mechanisms and outcomes. We propose a model by which these two activation pathways reside within the same tethering complex but remain insulated from one another. Structural modeling suggests a related mechanism for Sro7 activation of the exocyst in yeast and Ral GTPase activation of the exocyst in animal cells.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Allosteric Regulation, Animals, Cytoplasm, Exocytosis, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Vesicular Transport Proteins, rab GTP-Binding Proteins
Adaptor Proteins, Signal Transducing, Allosteric Regulation, Animals, Cytoplasm, Exocytosis, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Vesicular Transport Proteins, rab GTP-Binding Proteins
J Cell Biol
Date: Mar. 06, 2023
PubMed ID: 36729146
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