Cryo-EM structure of the β-1,3-glucan synthase FKS1-Rho1 complex

Journal article

β-1,3 Glucan synthase (GS) is essential for fungal cell wall biosynthesis. The GS holoenzyme comprises the glycosyltransferase FKS1 and its regulatory factor Rho1, a small GTPase. However, the mechanism by which Rho1 activates FKS1 in a GTP-dependent manner remains unclear. Here, we present two cryo-EM structures of FKS1, apo and in complex with Rho1. FKS1 adopts a cellulose synthase-like conformation. The interaction between Rho1 and FKS1 is enhanced in the presence of GTPγS. Rho1 is positioned within a pocket between the glycosyltransferase domain of FKS1 (GT domain) and the transmembrane helix spanning TM7-15. Comparison of the two structures reveals extensive conformational changes within FKS1. These alterations suggest that Rho1's GTP/GDP cycling may act as a molecular pump, promoting a dynamic transition between the resting and active states of FKS1. Notably, Rho1 triggers FKS1 conformational changes that may push the growing glucan chain into FKS1's transmembrane channel, thereby facilitating β-1,3-glucan elongation.

Authors: Li, J; Liu, H; Li, J; Liu, J; Dai, X

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 16
• Issue: 1
• Pages: 2054-2054
• Publication date: 2025-02-28
• DOI: 10.1038/s41467-025-57152-7
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: Chemistry; Biochemistry; ATP synthase; Enzyme