The extended apolar face of such a helix is optimized for interactions with apolar lipid moieties while the polar face can interact with phospholipid head groups and solvent molecules. The common lipid surface-binding motif found in many proteins, including apolipoproteins, perilipin, synucleins, CTT and PGK, is amphipathic α-helix comprised of 11-mer sequence repeats (( 5, 6) and references therein). The binding depends on the structural and physicochemical properties of both proteins and lipids and is facilitated by the hydrophobic defects on the lipid surface that form primary protein binding sites ( 1– 4). Protein binding to phospholipid surface is an important step in many biological reactions including apolipoprotein exchange among plasma lipoproteins, activation of lipid-regulated enzymes such as phosphoglycerate kinase (PGK) or CTP:phosphocholine cytidylyltransferase (CCT), synuclein aggregation in Parkinson’s disease, lipid storage in adypocytes, and binding of antimicrobial peptides to cell surfaces. This positive cooperativity in α-helical binding to phospholipid surface, which may result from direct and/or lipid-mediated protein-protein interactions, may be important for lipoprotein metabolism and for protein-membrane binding. However, if hydrophobic defects are limited, protein binding and insertion is aided by other surface-bound proteins and depends on their helical propensity: the larger the propensity the faster the binding and the broader its temperature range. at the lipid phase boundary), protein insertion into these defects is independent of the secondary structure in solution. Consequently, if the packing defects at the phospholipid surface are readily available (e.g. Interestingly, at T c=24 ☌ of the DMPC gel-to-liquid crystal transition, the clearance rate is independent of the protein helical content. Lipoprotein reconstitution upon cooling from the heat-denatured state and DMPC clearance studies revealed that protein secondary structure in solution and on DMPC correlates strongly with the maximal temperature of lipoprotein reconstitution: more helical proteins can reconstitute lipoproteins at higher temperatures. Thermal denaturation revealed that lipoprotein stability correlates weakly with the protein helix content: proteins with higher α-helical content on DMPC may form more stable complexes.
Dmpc and dmpc pro pro#
To understand the role of α-helical structure in protein-lipid interactions, we used discoidal lipoproteins reconstituted from dimyristoyl phosphatidylcholine (DMPC) and human apolipoprotein C-I (apoC-I, 6 kD) or its mutants containing single Pro substitutions along the sequence and differing in their α-helical content in solution (0–48%) and on DMPC (40–75%).
Protein binding to phospholipid surface is commonly mediated by amphipathic α-helices.
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