title: Core side-chain packing and backbone conformation in Lpp-56 coiled-coil mutants.
abstract: Native proteins exhibit precise geometric packing of atoms in their hydrophobic interiors. Nonetheless, controversy remains about the role of core side-chain packing in specifying and stabilizing the folded structures of proteins. Here we investigate the role of core packing in determining the conformation and stability of the Lpp-56 trimerization domain. The X-ray crystal structures of Lpp-56 mutants with alanine substitutions at two and four interior core positions reveal trimeric coiled coils in which the twist of individual helices and the helix-helix spacing vary significantly to achieve the most favored superhelical packing arrangement. Introduction of each alanine "layer" into the hydrophobic core destabilizes the superhelix by 1.4 kcal mol(-1). Although the methyl groups of the alanine residues pack at their optimum van der Waals contacts in the coiled-coil trimer, they provide a smaller component of hydrophobic interactions than bulky hydrophobic side-chains to the thermodynamic stability. Thus, specific side-chain packing in the hydrophobic core of coiled coils are important determinants of protein main-chain conformation and stability.
authors.affiliation: Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Min
authors.initials: M
authors.lastname: Lu
mesh_terms: D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004355:Drug Stability; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics; D008074:Lipoproteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D055672:Static Electricity
chemical_list: D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D008074:Lipoproteins; C099932:Lpp protein, E coli; D011994:Recombinant Proteins; D000409:Alanine