title: Biogenesis, transport and remodeling of lysophospholipids in Gram-negative bacteria.
abstract: Lysophospholipids (LPLs) are metabolic intermediates in bacterial phospholipid turnover. Distinct from their diacyl counterparts, these inverted cone-shaped molecules share physical characteristics of detergents, enabling modification of local membrane properties such as curvature. The functions of LPLs as cellular growth factors or potent lipid mediators have been extensively demonstrated in eukaryotic cells but are still undefined in bacteria. In the envelope of Gram-negative bacteria, LPLs are derived from multiple endogenous and exogenous sources. Although several flippases that move non-glycerophospholipids across the bacterial inner membrane were characterized, lysophospholipid transporter LplT appears to be the first example of a bacterial protein capable of facilitating rapid retrograde translocation of lyso forms of glycerophospholipids across the cytoplasmic membrane in Gram-negative bacteria. LplT transports lyso forms of the three bacterial membrane phospholipids with comparable efficiency, but excludes other lysolipid species. Once a LPL is flipped by LplT to the cytoplasmic side of the inner membrane, its diacyl form is effectively regenerated by the action of a peripheral enzyme, acyl-ACP synthetase/LPL acyltransferase (Aas). LplT-Aas also mediates a novel cardiolipin remodeling by converting its two lyso derivatives, diacyl or deacylated cardiolipin, to a triacyl form. This coupled remodeling system provides a unique bacterial membrane phospholipid repair mechanism. Strict selectivity of LplT for lyso lipids allows this system to fulfill efficient lipid repair in an environment containing mostly diacyl phospholipids. A rocker-switch model engaged by a pair of symmetric ion-locks may facilitate alternating substrate access to drive LPL flipping into bacterial cells. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop.
authors.affiliation: Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston McGovern Medical School, 6431 Fannin Street, Houston, TX 77030, USA. Electronic address: lei.zheng@uth.tmc.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston McGovern Medical School, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston McGovern Medical School, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Lu
authors.affiliation: Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston McGovern Medical School, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Jiazhe
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston McGovern Medical School, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Bogdanov
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001692:Biological Transport; D019730:Carbon-Sulfur Ligases / Q000737:chemistry / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism*; D006090:Gram-Negative Bacteria / Q000378:metabolism*; D050155:Lipogenesis; D008246:Lysophospholipids / Q000096:biosynthesis* / Q000737:chemistry; D049294:Phospholipid Transfer Proteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D008246:Lysophospholipids; D049294:Phospholipid Transfer Proteins; D019730:Carbon-Sulfur Ligases; C018749:long-chain-fatty-acid-(acyl-carrier-protein) ligase
keywords: Bacterial lipid; Flippase; LplT; Lysophospholipid; Membrane; Remodeling