title: Knr4: a disordered hub protein at the heart of fungal cell wall signalling.
abstract: The most highly connected proteins in protein-protein interactions networks are called hubs; they generally connect signalling pathways. In Saccharomyces cerevisiae, Knr4 constitutes a connecting node between the two main signal transmission pathways involved in cell wall maintenance upon stress: the cell wall integrity and the calcium-calcineurin pathway. Knr4 is required to enable the cells to resist many cell wall-affecting stresses, and KNR4 gene deletion is synthetic lethal with the simultaneous deletion of numerous other genes involved in morphogenesis and cell wall biogenesis. Knr4 has been shown to engage in multiple physical interactions, an ability conferred by the intrinsic structural adaptability of major disordered regions present in the N-terminal and C-terminal parts of the protein. Taking all together, Knr4 is an intrinsically disordered hub protein. Available data from other fungi indicate the conservation of Knr4 homologs cellular function and localization at sites of polarized growth among fungal species, including pathogenic species. Because of their particular role in morphogenesis control and of their fungal specificity, these proteins could constitute interesting new pharmaceutical drug targets for antifungal combination therapy.
authors.affiliation: LISBP, Université Fédérale de Toulouse, CNRS, INRA, INSA, 135 Avenue de Rangueil, F-31077, Toulouse, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Martin-Yken
authors.affiliation: LISBP, Université Fédérale de Toulouse, CNRS, INRA, INSA, 135 Avenue de Rangueil, F-31077, Toulouse, France.
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: François
authors.affiliation: LISBP, Université Fédérale de Toulouse, CNRS, INRA, INSA, 135 Avenue de Rangueil, F-31077, Toulouse, France.|Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, F-31077, Toulouse, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Zerbib
mesh_terms: D059447:Cell Cycle Checkpoints; D002473:Cell Wall / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: C085451:SMI1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors