title: The membrane- and soluble-protein helix-helix interactome: similar geometry via different interactions.
abstract: α Helices are a basic unit of protein secondary structure and therefore the interaction between helices is crucial to understanding tertiary and higher-order folds. Comparing subtle variations in the structural and sequence motifs between membrane and soluble proteins sheds light on the different constraints faced by each environment and elucidates the complex puzzle of membrane protein folding. Here, we demonstrate that membrane and water-soluble helix pairs share a small number of similar folds with various interhelical distances. The composition of the residues that pack at the interface between corresponding motifs shows that hydrophobic residues tend to be more enriched in the water-soluble class of structures and small residues in the transmembrane class. The latter group facilitates packing via sidechain- and backbone-mediated hydrogen bonds within the low-dielectric membrane milieu. The helix-helix interactome space, with its associated sequence preferences and accompanying hydrogen-bonding patterns, should be useful for engineering, prediction, and design of protein structure.
authors.affiliation: Department of Physics and Astronomy, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Shao-Qing
authors.initials: SQ
authors.lastname: Zhang
authors.affiliation: Graduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Kulp
authors.affiliation: Graduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Chaim A
authors.initials: CA
authors.lastname: Schramm
authors.affiliation: Graduate Program in Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Mravic
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: ilan.samish@weizmann.ac.il.
authors.forename: Ilan
authors.initials: I
authors.lastname: Samish
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: william.degrado@ucsf.edu.
authors.forename: William F
authors.initials: WF
authors.lastname: DeGrado
mesh_terms: D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D012995:Solubility; D040681:Structural Homology, Protein
chemical_list: D008565:Membrane Proteins