A molecular mechanism for membrane chaperoning by a late embryogenesis abundant protein

Li, X.-H.; Yu, C. W. H.; Gomez-Navarro, N.; Stancheva, V.; Zhu, H.; Guibao, C.; Xie, B.; Murthy, A.; Wozny, M.; Leslie, B.; Kaminski, M.; Malhotra, K.; Johnson, C. M.; Blackledge, M.; Santhanam, B.; Green, D. R.; Peng, J.; Liu, W.; Huang, J.; Miller, E. A.; Freund, S. M. V.; Babu, M. M.

doi:10.1101/2022.07.29.502075

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bioRxiv · 10.1101/2022.07.29.502075

A molecular mechanism for membrane chaperoning by a late embryogenesis abundant protein

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Abstract

Environmental stress can result in substantial damage to proteins, membranes, and genetic material, impacting organismal survival1-3. Stress tolerance can be conferred by intrinsically disordered proteins (IDPs)4 that lack stable tertiary structure. IDPs from the large family of late embryogenesis abundant (LEA) proteins confer a fitness advantage when heterologously expressed5,6. Such protection suggests a general molecular function leading to stress tolerance, although the mechanisms remain unclear. Here, we report that a tardigrade LEA protein that confers stress tolerance in yeast acts as a molecular chaperone for the mitochondrial membrane. This protein, named HeLEA1, localizes to the mitochondrial matrix, and harbors conserved LEA sequence motifs that undergo dynamic disorder-to-helical transition upon binding to negatively charged membranes. Yeast expressing HeLEA1 show increased mitochondrial membrane fluidity, increased membrane potential, and enhanced tolerance to hyperosmotic stress under non-fermentative growth without significantly altering mitochondrial lipid composition or triggering a generic stress response. We demonstrate that membrane binding ameliorates excess surface tension, possibly by stabilizing lipid packing defects. Evolutionary analysis suggests that HeLEA1 homologs localize to different membrane-bound organelles and share similar sequence and biophysical features. We suggest that membrane chaperoning by LEA proteins represents a general biophysical solution that can operate across the domains of life.

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Li, X.-H., Yu, C. W. H., Gomez-Navarro, N., Stancheva, V., Zhu, H., Guibao, C., Xie, B., Murthy, A., Wozny, M., Leslie, B., Kaminski, M., Malhotra, K., Johnson, C. M., Blackledge, M., Santhanam, B., Green, D. R., Peng, J., Liu, W., Huang, J., Miller, E. A., Freund, S. M. V., Babu, M. M.. 2022-07-31. A molecular mechanism for membrane chaperoning by a late embryogenesis abundant protein. https://doi.org/10.1101/2022.07.29.502075

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