A Novel Superfamily of Bridge-like Lipid Transfer Proteins

Overview

Journal Trends Cell Biol

Specialty Cell Biology

Date 2022 May 1

PMID 35491307

Authors

Sarah D Neuman

Tim P Levine

Arash Bashirullah

Affiliations

Soon will be listed here.

Abstract

Lipid transfer proteins mediate nonvesicular transport of lipids at membrane contact sites to regulate the lipid composition of organelle membranes. Recently, a new type of bridge-like lipid transfer protein has emerged; these proteins contain a long hydrophobic groove and can mediate bulk transport of lipids between organelles. Here, we review recent insights into the structure of these proteins and identify a repeating modular unit that we propose to name the repeating β-groove (RBG) domain. This new structural understanding conceptually unifies all the RBG domain-containing lipid transfer proteins as members of an RBG protein superfamily. We also examine the biological functions of these lipid transporters in normal physiology and disease and speculate on the evolutionary origins of RBG proteins in bacteria.

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References

Tamura N, Nishimura T, Sakamaki Y, Koyama-Honda I, Yamamoto H, Mizushima N . Differential requirement for ATG2A domains for localization to autophagic membranes and lipid droplets. FEBS Lett. 2017; 591(23):3819-3830. DOI: 10.1002/1873-3468.12901. View

Yeshaw W, van der Zwaag M, Pinto F, Lahaye L, Faber A, Gomez-Sanchez R . Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility. Elife. 2019; 8. PMC: 6389287. DOI: 10.7554/eLife.43561. View

Yang J, Anishchenko I, Park H, Peng Z, Ovchinnikov S, Baker D . Improved protein structure prediction using predicted interresidue orientations. Proc Natl Acad Sci U S A. 2020; 117(3):1496-1503. PMC: 6983395. DOI: 10.1073/pnas.1914677117. View

Wirtz K, ZILVERSMIT D . Exchange of phospholipids between liver mitochondria and microsomes in vitro. J Biol Chem. 1968; 243(13):3596-602. View

Cheng X, Bezanilla M . SABRE populates ER domains essential for cell plate maturation and cell expansion influencing cell and tissue patterning. Elife. 2021; 10. PMC: 7987345. DOI: 10.7554/eLife.65166. View

Samaranayake H, Cowan A, Klobutcher L . Vacuolar protein sorting protein 13A, TtVPS13A, localizes to the tetrahymena thermophila phagosome membrane and is required for efficient phagocytosis. Eukaryot Cell. 2011; 10(9):1207-18. PMC: 3187053. DOI: 10.1128/EC.05089-11. View

Jones D, Thornton J . The impact of AlphaFold2 one year on. Nat Methods. 2022; 19(1):15-20. DOI: 10.1038/s41592-021-01365-3. View

Smertenko A, Assaad F, Baluska F, Bezanilla M, Buschmann H, Drakakaki G . Plant Cytokinesis: Terminology for Structures and Processes. Trends Cell Biol. 2017; 27(12):885-894. DOI: 10.1016/j.tcb.2017.08.008. View

Procissi A, Guyon A, Pierson E, Giritch A, Knuiman B, Grandjean O . KINKY POLLEN encodes a SABRE-like protein required for tip growth in Arabidopsis and conserved among eukaryotes. Plant J. 2003; 36(6):894-904. DOI: 10.1046/j.1365-313x.2003.01933.x. View

10.

Shen H, Leyton D, Shiota T, Belousoff M, Noinaj N, Lu J . Reconstitution of a nanomachine driving the assembly of proteins into bacterial outer membranes. Nat Commun. 2014; 5:5078. PMC: 4633281. DOI: 10.1038/ncomms6078. View

11.

Koike S, Jahn R . SNAREs define targeting specificity of trafficking vesicles by combinatorial interaction with tethering factors. Nat Commun. 2019; 10(1):1608. PMC: 6453939. DOI: 10.1038/s41467-019-09617-9. View

12.

Verstreken P, Ohyama T, Haueter C, Habets R, Lin Y, Swan L . Tweek, an evolutionarily conserved protein, is required for synaptic vesicle recycling. Neuron. 2009; 63(2):203-15. PMC: 2759194. DOI: 10.1016/j.neuron.2009.06.017. View

13.

Otomo T, Chowdhury S, Lander G . The rod-shaped ATG2A-WIPI4 complex tethers membranes in vitro. Contact (Thousand Oaks). 2019; 1. PMC: 6372110. DOI: 10.1177/2515256418819936. View

14.

Kolehmainen J, Black G, Saarinen A, Chandler K, Clayton-Smith J, Traskelin A . Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport. Am J Hum Genet. 2003; 72(6):1359-69. PMC: 1180298. DOI: 10.1086/375454. View

15.

Otto G, Razi M, Morvan J, Stenner F, Tooze S . A novel syntaxin 6-interacting protein, SHIP164, regulates syntaxin 6-dependent sorting from early endosomes. Traffic. 2010; 11(5):688-705. DOI: 10.1111/j.1600-0854.2010.01049.x. View

16.

Park J, Thorsness M, Policastro R, McGoldrick L, Hollingsworth N, Thorsness P . Yeast Vps13 promotes mitochondrial function and is localized at membrane contact sites. Mol Biol Cell. 2016; 27(15):2435-49. PMC: 4966984. DOI: 10.1091/mbc.E16-02-0112. View

17.

Castro I, Shortill S, Dziurdzik S, Cadou A, Ganesan S, Valenti R . Systematic analysis of membrane contact sites in uncovers modulators of cellular lipid distribution. Elife. 2022; 11. PMC: 9648973. DOI: 10.7554/eLife.74602. View

18.

Hochholdinger F, Yu P, Marcon C . Genetic Control of Root System Development in Maize. Trends Plant Sci. 2017; 23(1):79-88. DOI: 10.1016/j.tplants.2017.10.004. View

19.

Anding A, Wang C, Chang T, Sliter D, Powers C, Hofmann K . Vps13D Encodes a Ubiquitin-Binding Protein that Is Required for the Regulation of Mitochondrial Size and Clearance. Curr Biol. 2018; 28(2):287-295.e6. PMC: 5787036. DOI: 10.1016/j.cub.2017.11.064. View

20.

Ghanbarpour A, Valverde D, Melia T, Reinisch K . A model for a partnership of lipid transfer proteins and scramblases in membrane expansion and organelle biogenesis. Proc Natl Acad Sci U S A. 2021; 118(16). PMC: 8072408. DOI: 10.1073/pnas.2101562118. View