An Amino Acid Packing Code for α-Helical Structure and Protein Design

Joo, Hyun; Chavan, Archana G.; Phan, J.; Day, Ryan; Tsai, Jerry

doi:10.1016/j.jmb.2012.03.004

Cited by 23 publications

(73 citation statements)

References 121 publications

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“…In summary, the geometries of most tightly interacting helices are well represented by the centroids of clusters 1–7 (Figure 2), which we will discuss in detail below. Interestingly, Joo et al datamined sets of residues that contact each other and computed the crossing angles of the corresponding helices (Joo et al, 2012). Plotting the histogram distribution of these angles results in discrete peaks corresponding to the packing states described here (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

The Membrane- and Soluble-Protein Helix-Helix Interactome: Similar Geometry via Different Interactions

et al. 2015

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Summary Alpha-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 accompanied hydrogen-bonding patterns, should be useful for protein structure engineering, prediction and design.

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Section: Resultsmentioning

confidence: 99%

The Membrane- and Soluble-Protein Helix-Helix Interactome: Similar Geometry via Different Interactions

et al. 2015

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“…The knob-socket model (Joo et al, 2012) based helix predictions were used to refine the boundaries of helices in the predicted secondary structure of the protein. Using amino acid preferences for the knobs, the packing interactions between helix 2 (35-43) and helix 3 (62-76) were predicted by socket patterns on each helix.…”

Section: Methodsmentioning

confidence: 99%

The effect of α-mating factor secretion signal mutations on recombinant protein expression in Pichia pastoris

Lin-Cereghino

Stark

Kim

et al. 2013

Gene

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102

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The methylotrophic yeast, Pichia pastoris, has been genetically engineered to produce many heterologous proteins for industrial and research purposes. In order to secrete proteins for easier purification from the extracellular medium, the coding sequence of recombinant proteins are initially fused to the Saccharomyces cerevisiae α-mating factor secretion signal leader. Extensive site-directed mutagenesis of the prepro region of the α-mating factor secretion signal sequence was performed in order to determine the effects of various deletions and substitutions on expression. Though some mutations clearly dampened protein expression, deletion of amino acids 57-70, corresponding to the predicted 3rd alpha helix of α-mating factor secretion signal, increased secretion of reporter proteins horseradish peroxidase and lipase at least 50% in small-scale cultures. These findings raise the possibility that the secretory efficiency of the leader can be further enhanced in the future.

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“…Taken together, these observations at first suggest that regions of the protein with many two or three residue cliques are poorly packed and more sensitive to changes in sequence. Based on a new analysis 34 , isolated changes in two and three residue cliques occurs in less than 9% of the cases for two and three body cliques. The 91% majority of changes in two and three body cliques results from repacking and rearrangements of three and four body clique packing.…”

Section: Results / Discussionmentioning

confidence: 98%

“…To this end, a recent development in our group has the characterization of a basic principle underlying protein packing of knobs into sockets that allows us to identify the amino acid code for protein structure 34 . The knob-socket construct allows us to identify the exact changes in packing between the template and native structure that need to be modeled.…”

Section: Resultsmentioning

confidence: 99%

Understanding the general packing rearrangements required for successful template based modeling of protein structure from a CASP experiment

Day

Joo

Chavan

et al. 2013

Computational Biology and Chemistry

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As an alternative to the common template based protein structure prediction methods based on main-chain position, a novel side-chain centric approach has been developed. Together with a Bayesian loop modeling procedure and a combination scoring function, the Stone Soup algorithm was applied to the CASP9 set of template based modeling targets. Although the method did not generate as large of perturbations to the template structures as necessary, the analysis of the results gives unique insights into the differences in packing between the target structures and their templates. Considerable variation in packing is found between target and template structures even when the structures are close, and this variation is found due to 2 and 3 body packing interactions. Outside the inherent restrictions in packing representation of the PDB, the first steps in correctly defining those regions of variable packing have been mapped primarily to local interactions, as the packing at the secondary and tertiary structure are largely conserved. Of the scoring functions used, a loop scoring function based on water structure exhibited some promise for discrimination. These results present a clear structural path for further development of a side-chain centered approach to template based modeling.

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An Amino Acid Packing Code for α-Helical Structure and Protein Design

Cited by 23 publications

References 121 publications

The Membrane- and Soluble-Protein Helix-Helix Interactome: Similar Geometry via Different Interactions

The Membrane- and Soluble-Protein Helix-Helix Interactome: Similar Geometry via Different Interactions

The effect of α-mating factor secretion signal mutations on recombinant protein expression in Pichia pastoris

Understanding the general packing rearrangements required for successful template based modeling of protein structure from a CASP experiment

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