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Stoichiometry of lipid interactions with transmembrane proteins—Deduced from the 3D structures
Author(s) -
Páli Tibor,
Bashtovyy Denys,
Marsh Derek
Publication year - 2006
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.052021406
Subject(s) - integral membrane protein , chemistry , membrane protein , transmembrane protein , crystallography , lipid bilayer , protein structure , population , protein folding , biophysics , membrane , biochemistry , biology , receptor , demography , sociology
The stoichiometry of the first shell of lipids interacting with a transmembrane protein is defined operationally by the population of spin‐labeled lipid chains whose motion is restricted directly by the protein. Interaction stoichiometries have been determined experimentally for a wide range of α‐helical integral membrane proteins by using spin‐label ESR spectroscopy. Here, we determine the spatially defined number of first‐shell lipids at the hydrophobic perimeter of integral membrane proteins whose 3D structure has been determined by X‐ray crystallography and lipid–protein interactions characterized by spin‐labeling. Molecular modeling is used to build a single shell of lipids surrounding transmembrane structures derived from the PDB. Constrained energy optimization of the protein–lipid assemblies is performed by molecular mechanics. For relatively small proteins (up to 7–12 transmembrane helices), the geometrical first shell corresponds to that defined experimentally by perturbation of the lipid‐chain dynamics. For larger, multi‐subunit α‐helical proteins, the lipids perturbed directly by the protein may either exceed or be less in number than those that can be accommodated at the intramembranous perimeter. In these latter cases, the motionally restricted spin‐labeled lipids can be augmented by intercalation, or can correspond to a specific subpopulation at the protein interface, respectively. For monomeric β‐barrel proteins, the geometrical lipid stoichiometry corresponds to that determined from lipid mobility for a 22‐stranded barrel, but fewer lipids are motionally restricted than can be accommodated around an eight‐stranded barrel. Deviations from the geometrical first shell, in the β‐barrel case, are for the smaller protein with a highly curved barrel.

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