A knowledge-based potential highlights unique features of membrane α-helical and β-barrel protein insertion and folding.
ABSTRACT Outer membrane β-barrel proteins differ from α-helical inner membrane proteins in lipid environment, secondary structure, and the proposed processes of folding and insertion. It is reasonable to expect that outer membrane proteins may contain primary sequence information specific for their folding and insertion behavior. In previous work, a depth-dependent insertion potential, E(z) , was derived for α-helical inner membrane proteins. We have generated an equivalent potential for TM β-barrel proteins. The similarities and differences between these two potentials provide insight into unique aspects of the folding and insertion of β-barrel membrane proteins. This potential can predict orientation within the membrane and identify functional residues involved in intermolecular interactions.
Article: Reconstitution of Channel Proteins in (Polymerized) ABA Triblock Copolymer Membranes This work was supported by the Swiss National Science Foundation. We thank Dr. T. Hirt and Dr. J. Leukel for the synthesis of the triblock copolymer, Dr. P. Van Gelder and Dr. F. Dumas for bright and helpful discussions, and T. Haefele for his contribution to the experimental part.Angewandte Chemie International Edition 01/2001; 39(24):4599-4602. · 13.45 Impact Factor
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ABSTRACT: Glycine is an intrinsically destabilizing residue in beta sheets. In natural proteins, however, this destabilization can be 'rescued' by specific cross-strand pairing with aromatic residues. Here, we present an experimental study of this effect. Protein variants containing glycine and aromatic residues positioned across beta strands in both antiparallel and parallel orientations were studied. The pairing of glycine and phenylalanine across antiparallel strands resulted in a synergistic increase in protein stability. Dramatic differences in stability were observed for the parallel beta-sheet mutants, which were dependent upon the type of site occupied by glycine as well as the type of aromatic residue with which it was cross-strand paired. Experimental results from a series of mutants suggest a thermodynamic benefit for glycine-aromatic pairing across antiparallel beta strands, consistent with the prevalence of such pairs in natural proteins. We also demonstrate the specificity of glycine-aromatic interactions across parallel beta strands, which defines strand register.Folding and Design 02/1998; 3(6):449-55.
Article: Interstrand pairing patterns in beta-barrel membrane proteins: the positive-outside rule, aromatic rescue, and strand registration prediction.[show abstract] [hide abstract]
ABSTRACT: beta-Barrel membrane proteins are found in the outer membrane of Gram-negative bacteria, mitochondria, and chloroplasts. Little is known about how residues in membrane beta-barrels interact preferentially with other residues on adjacent strands. We have developed probabilistic models to quantify propensities of residues for different spatial locations and for interstrand pairwise contact interactions involving strong H-bonds, side-chain interactions, and weak H-bonds. Using the reference state of exhaustive permutation of residues within the same beta-strand, the propensity values and p-values measuring statistical significance are calculated exactly by analytical formulae we have developed. Our findings show that there are characteristic preferences of residues for different membrane locations. Contrary to the "positive-inside" rule for helical membrane proteins, beta-barrel membrane proteins follow a significant albeit weaker "positive-outside" rule, in that the basic residues Arg and Lys are disproportionately favored in the extracellular cap region and disfavored in the periplasmic cap region. We find that different residue pairs prefer strong backbone H-bonded interstrand pairings (e.g. Gly-aromatic) or non-H-bonded pairings (e.g. aromatic-aromatic). In addition, we find that Tyr and Phe participate in aromatic rescue by shielding Gly from polar environments. We also show that these propensities can be used to predict the registration of strand pairs, an important task for the structure prediction of beta-barrel membrane proteins. Our accuracy of 44% is considerably better than random (7%). It also significantly outperforms a comparable registration prediction for soluble beta-sheets under similar conditions. Our results imply several experiments that can help to elucidate the mechanisms of in vitro and in vivo folding of beta-barrel membrane proteins. The propensity scales developed in this study will also be useful for computational structure prediction and for folding simulations.Journal of Molecular Biology 01/2006; 354(4):979-93. · 4.00 Impact Factor