8AJ2

structure of the ordered core of Knr4 (loop 189-217 deleted)

8AJ2 の概要

• エントリーDOI: 10.2210/pdb8aj2/pdb
• 関連するPDBエントリー: 5J1B
• 分子名称: Structured core of Knr4 (2 entities in total)
• 機能のキーワード: cell-wall integrity stress response beta-glucan synthesis, signaling protein
• 由来する生物種: Saccharomyces cerevisiae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55633.36

構造登録者

Caisso, A.,Donker, E.I.M.,Maveyraud, L.,Zerbib, D. (登録日: 2022-07-27, 公開日: 2023-04-26, 最終更新日: 2024-02-07)

主引用文献

Batista, M.,Donker, E.I.M.,Bon, C.,Guillien, M.,Caisso, A.,Mourey, L.,Francois, J.M.,Maveyraud, L.,Zerbib, D.
The Conserved Yeast Protein Knr4 Involved in Cell Wall Integrity Is a Multi-domain Intrinsically Disordered Protein.
J.Mol.Biol., 435:168048-168048, 2023

PubMed Abstract: Knr4/Smi1 proteins are specific to the fungal kingdom and their deletion in the model yeast Saccharomyces cerevisiae and the human pathogen Candida albicans results in hypersensitivity to specific antifungal agents and a wide range of parietal stresses. In S. cerevisiae, Knr4 is located at the crossroads of several signalling pathways, including the conserved cell wall integrity and calcineurin pathways. Knr4 interacts genetically and physically with several protein members of those pathways. Its sequence suggests that it contains large intrinsically disordered regions. Here, a combination of small-angle X-ray scattering (SAXS) and crystallographic analysis led to a comprehensive structural view of Knr4. This experimental work unambiguously showed that Knr4 comprises two large intrinsically disordered regions flanking a central globular domain whose structure has been established. The structured domain is itself interrupted by a disordered loop. Using the CRISPR/Cas9 genome editing technique, strains expressing KNR4 genes deleted from different domains were constructed. The N-terminal domain and the loop are essential for optimal resistance to cell wall-binding stressors. The C-terminal disordered domain, on the other hand, acts as a negative regulator of this function of Knr4. The identification of molecular recognition features, the possible presence of secondary structure in these disordered domains and the functional importance of the disordered domains revealed here designate these domains as putative interacting spots with partners in either pathway. Targeting these interacting regions is a promising route to the discovery of inhibitory molecules that could increase the susceptibility of pathogens to the antifungals currently in clinical use.

PubMed: 36933821
DOI: 10.1016/j.jmb.2023.168048

実験手法

X-RAY DIFFRACTION (2.2 Å)