7pz2
From Proteopedia
Structure of the mechanosensor domain of Wsc1 from Saccharomyces cerevisiae
Structural highlights
FunctionSLG1_YEAST Plays a role during G1 to regulate entering or exiting the cell cycle. Involved in stress responses. Has a role in cell wall integrity signaling. Activates ROM1 or ROM2 catalyzed guanine nucleotide exchange toward RHO1. Important regulator of the actin cytoskeleton rearrangements in conditions of cell wall expansion and membrane stretching. Specifically required for the actin reorganization induced by hypo-osmotic shock. Multicopy suppressor of 1,3-beta-glucan synthase (GS). Activates GS upstream of RHO1. Acts positively on the PKC1-MAPK pathway. Activates transiently SLT2 during alkaline stress, which leads to an increase in the expression of several specific genes.[1] [2] [3] [4] [5] Publication Abstract from PubMedIn the yeast Saccharomyces cerevisiae and other ascomycetes, the maintenance of cell wall integrity is governed by a family of plasma-membrane spanning sensors that include the Wsc-type proteins. These cell wall proteins apparently sense stress-induced mechanical forces at the cell surface and target the cell wall integrity (CWI) signaling pathway, but the structural base for their sensor function is yet unknown. Here, we solved a high-resolution crystal structure of the extracellular cysteine-rich domain (CRD) of yeast Wsc1, which shows the characteristic PAN/Apple domain fold with two of the four Wsc1 disulfide bridges being conserved in other PAN domain cores. Given the general function of PAN domains in mediating protein-protein and protein-carbohydrate interactions, this finding underpins the importance of Wsc domains in conferring sensing and localization functions. Our Wsc1 CRD structure reveals an unusually high number of surface-exposed aromatic residues that are conserved in other fungal CRDs, and can be arranged into three solvent-exposed clusters. Mutational analysis demonstrates that two of the aromatic clusters are required for conferring S. cerevisiae Wsc1-dependent resistance to the glucan synthase inhibitor caspofungin, and the chitin-binding agents Congo red and Calcofluor white. These findings suggest an essential role of surface-exposed aromatic clusters in fungal Wsc-type sensors that might include an involvement in stress-induced sensor-clustering required to elicit appropriate cellular responses via the downstream CWI pathway. Structure of the Yeast Cell Wall Integrity Sensor Wsc1 Reveals an Essential Role of Surface-Exposed Aromatic Clusters.,Schoppner P, Lutz AP, Lutterbach BJ, Bruckner S, Essen LO, Mosch HU J Fungi (Basel). 2022 Apr 8;8(4):379. doi: 10.3390/jof8040379. PMID:35448610[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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