PT  - JOURNAL ARTICLE
AU  - Makarova, Maria
AU  - Peter, Maria
AU  - Balogh, Gabor
AU  - Glatz, Attila
AU  - MacRae, James I.
AU  - Mora, Nestor Lopez
AU  - Booth, Paula
AU  - Makeyev, Eugene
AU  - Vigh, Laszlo
AU  - Oliferenko, Snezhana
TI  - Delineating the rules for structural adaptation of membrane-associated proteins to evolutionary changes in membrane lipidome
AID  - 10.1101/762146
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 762146
4099  - http://biorxiv.org/content/early/2019/09/09/762146.short
4100  - http://biorxiv.org/content/early/2019/09/09/762146.full
AB  - Membrane function is fundamental to life. Each species explores membrane lipid diversity within a genetically predefined range of possibilities. How membrane lipid composition in turn defines the functional space available for evolution of membrane-centered processes remains largely unknown. We address this fundamental question using related fission yeasts Schizosaccharomyces pombe and Schizosaccharomyces japonicus. We show that unlike S. pombe that generates membranes where both glycerophospholipid acyl tails are predominantly 16-18 carbons long, S. japonicus synthesizes unusual ‘asymmetrical’ glycerophospholipids where the tails differ in length by 6-8 carbons. This results in stiffer bilayers with distinct lipid packing properties. Retroengineered S. pombe synthesizing the S. japonicus-type phospholipids exhibits unfolded protein response and downregulates secretion. Importantly, our protein sequence comparisons and domain swap experiments indicate that transmembrane helices co-evolve with membranes, suggesting that, on the evolutionary scale, changes in membrane lipid composition may necessitate extensive adaptation of the membrane-associated proteome.