Discovery of a Novel Quality Control Mechanism That Assists Membrane Protein Folding

July 14, 2026

Resolving the Trade-off Between Structural Stability and Function

Researchers from Nagoya University, in collaboration with Nagaoka University of Technology, the University of Toronto, RIKEN CSRS, the University of Pennsylvania, the University of Lausanne, Hokkaido University, the University of Tokyo, Yamagata University, and Kyoto University, have discovered a previously unknown mechanism that assists the folding of transmembrane proteins.

Transmembrane proteins are essential for transporting molecules and signals across biological membranes, but hydrophilic residues within their membrane-spanning regions can destabilize their structure.
The yeast glucan synthase Fks1 requires numerous hydrophilic residues within its transmembrane region to transport glucan across the membrane, creating a trade-off between structural stability and function.
The research group discovered that the endoplasmic reticulum (ER) protein Pbr1 binds to newly synthesized Fks1, assists its folding, and promotes its export from the ER, revealing a previously unknown ER quality control mechanism.

These findings could contribute to the development of new antifungal therapies.

 

Original article

Proceedings of the National Academy of Sciences of the United States of America
DOI: 10.1073/pnas.2612792123

K. Obara, H. Okada, G. Tand, S. Ohnuki, G. Suzuki, H. Ohtake, K. Kubo, F. Ghanegolmohammadi, S. Ishizaka, Y. Yashiroda, A. Okita, E. Mishiro-Sato , K. Suzuki, Y. Tamura, R. Ashine, Y. Ikeda, T. Kamura, J. v. Leeuwen, B. Andrews, E. Bi, N. N. Noda, C. Boone, Y. Ohya,

"Role of Pbr1, a putative oxidoreductase in the ER quality-control and folding of yeast Fks1 glucan synthase".

Contact

Charles Boone: Team Director
Yoko Yashiroda; Deputy Team Director
Molecular Ligand Target Research Team