Delineating the Rules for Structural Adaptation of Membrane-Associated Proteins to Evolutionary Changes in Membrane Lipidome

TY - JOUR

T1 - Delineating the Rules for Structural Adaptation of Membrane-Associated Proteins to Evolutionary Changes in Membrane Lipidome

AU - Makarova, Maria

AU - Peter, Maria

AU - Balogh, Gabor

AU - Glatz, Attila

AU - MacRae, James I

AU - Lopez Mora, Nestor

AU - Booth, Paula

AU - Makeyev, Eugene

AU - Vigh, Laszlo

AU - Oliferenko, Snezhana

PY - 2020/2/3

Y1 - 2020/2/3

N2 - 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 support the hypothesis 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. Makarova et al. show that membranes of related fission yeasts S. pombe and S. japonicus are made of structurally distinct phospholipids because of the difference in fatty acid synthase activities. Bioinformatics and retro-engineering experiments reveal that evolutionary changes in lipid metabolism require adaptation of the membrane-associated proteome.

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 support the hypothesis 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. Makarova et al. show that membranes of related fission yeasts S. pombe and S. japonicus are made of structurally distinct phospholipids because of the difference in fatty acid synthase activities. Bioinformatics and retro-engineering experiments reveal that evolutionary changes in lipid metabolism require adaptation of the membrane-associated proteome.

KW - adaptation

KW - evolution

KW - fatty acid synthase

KW - fission yeasts

KW - lipid metabolism

KW - lipids

KW - membranes

KW - transmembrane proteins

KW - unfolded protein response

UR - http://www.scopus.com/inward/record.url?scp=85078487802&partnerID=8YFLogxK

U2 - 10.1016/j.cub.2019.11.043

DO - 10.1016/j.cub.2019.11.043

M3 - Article

C2 - 31956022

SN - 0960-9822

VL - 30

SP - 367-380.e8

JO - Current Biology

JF - Current Biology

IS - 3

ER -