Antimicrobial activity of apolipoprotein A-I It has been well established that the human serum protein apolipoprotein A-I (apoA-I) plays a central role in the transport and metabolism of cholesterol. However, it has become increasingly clear that the protein plays an important role in innate immunity as well. We propose to investigate the binding of apoA-I to bacterial membranes. Initial studies have shown that apoA-I binds to lipopolysaccharides of the outer membrane and negatively charged phospholipids of the inner membrane. Lysine residues play a critical role in this binding interaction.
We aim to understand the molecular basis for the antimicrobial properties of apoA-I. The binding of apoA-I to a variety of LPS from different bacterial sources including truncated LPS versions, and phospholipids from in inner membrane, will be investigated in detail. This will provide key insight into the binding mechanism. Since neutralization of lysine residues inhibits antimicrobial properties, we will use a naturally occurring modification caused by acrolein. This agent is abundantly present in cigarette smoke targeting lysine residues in serum proteins. Upon modification by acrolein, binding to lipopolysaccharides, negatively charged phospholipids, and the inhibition of bacterial growth will be determined. The proposed studies aims to better understand how apoA-I recognizes bacterial membrane surfaces thereby providing protection against gram-negative infection. The knowledge obtained by this study has the potential to result in improved ways to manage bacterial sepsis for which no effective treatment exists.

Public Health Relevance

Antimicrobial activity of apolipoprotein A-I Apolipoprotein A-I is an exchangeable apolipoprotein well known for its anti-atherogenic properties. It has become clear that the protein also plays a role in innate immunity and exerts antimicrobial properties. The proposal aims to understand the molecular basis of the antimicrobial activity. Knowledge obtained from our studies into this novel role of apolipoprotein A-I may lead to improved ways to treat gram-negative bacterial sepsis.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Continuance Award (SC3)
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Special Emphasis Panel (ZGM1)
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Rogers, Michael E
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California State University Long Beach
Schools of Arts and Sciences
Long Beach
United States
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Horn, James V C; Ellena, Rachel A; Tran, Jesse J et al. (2017) Transfer of C-terminal residues of human apolipoprotein A-I to insect apolipophorin III creates a two-domain chimeric protein with enhanced lipid binding activity. Biochim Biophys Acta Biomembr 1859:1317-1325
Ikon, Nikita; Shearer, Jennifer; Liu, Jianfang et al. (2017) A facile method for isolation of recombinant human apolipoprotein A-I from E. coli. Protein Expr Purif 134:18-24
Krishnamoorthy, Aparna; Witkowski, Andrzej; Tran, Jesse J et al. (2017) Characterization of secondary structure and lipid binding behavior of N-terminal saposin like subdomain of human Wnt3a. Arch Biochem Biophys 630:38-46
Sallee, Daniel E; Horn, James V C; Fuentes, Lukas A et al. (2017) Expression of the C-terminal domain of human apolipoprotein A-I using a chimeric apolipoprotein. Protein Expr Purif 137:13-19
Dwivedi, Pankaj; Rodriguez, Johana; Ibe, Nnejiuwa U et al. (2016) Deletion of the N- or C-Terminal Helix of Apolipophorin III To Create a Four-Helix Bundle Protein. Biochemistry 55:3607-15
Crowhurst, Karin A; Horn, James V C; Weers, Paul M M (2016) Backbone and side chain chemical shift assignments of apolipophorin III from Galleria mellonella. Biomol NMR Assign 10:143-7
Thistle, Jake; Martinon, Daisy; Weers, Paul M M (2015) Helix 1 tryptophan variants in Galleria mellonella apolipophorin III. Chem Phys Lipids 193:18-23
Beck, Wendy H J; Adams, Christopher P; Biglang-Awa, Ivan M et al. (2013) Apolipoprotein A-I binding to anionic vesicles and lipopolysaccharides: role for lysine residues in antimicrobial properties. Biochim Biophys Acta 1828:1503-10
Moreno-Habel, Daniela A; Biglang-awa, Ivan M; Dulce, Angelica et al. (2012) Inactivation of the budded virus of Autographa californica M nucleopolyhedrovirus by gloverin. J Invertebr Pathol 110:92-101
Oztug, Merve; Martinon, Daisy; Weers, Paul M M (2012) Characterization of the apoLp-III/LPS complex: insight into the mode of binding interaction. Biochemistry 51:6220-7

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