The origin of β-strand bending in globular proteins

Fujiwara, Kazuo; Ebisawa, Shinichi; Watanabe, Yuka; Fujiwara, Hiromi; Ikeguchi, Masamichi

doi:10.1186/s12900-015-0048-y

Cited by 18 publications

(23 citation statements)

References 27 publications

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“…The positive or negative sign of the local bend angle is the sign of the scalar product between the cross product

\overset{LM}{true} \times \overset{MN}{true}

and the perpendicular vector

\overset{{RC}_{α} ((), i + 1)}{true}

. The distributions of local bend angles were normalized by the following equation to account for differences in the number of cases of each angle, which is proportional to the circumference of the circle of radius sin| θ |

N^{'} = \frac{N}{sin (()||, {normalθ}^{bend})}

…”

Section: Methodsmentioning

confidence: 99%

“…We concluded that the side chains of these residues influence the relative strength of inter‐strand hydrogen bonds, thereby suppressing β‐strand twisting and bending for WS proteins. Furthermore, we investigated the origin of β‐strand bending for WS proteins and found that the main driving force for full‐length β‐strand bending is hydrophobic interactions involving aromatic residues, whereas that for local β‐strand bending is hydrophobic interactions involving aliphatic residues …”

Section: Introductionmentioning

confidence: 99%

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β‐Strand twisting/bending in soluble and transmembrane β‐barrel structures

2018

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The majority of β-strands in globular proteins have a right-handed twist and bend. The dominant driving force for β-strand twisting is thought to be inter-strand hydrogen bonds. We previously demonstrated that for water-soluble proteins, both the twisting and bending of β-strand are suppressed by the polar side chains of serine, threonine, and asparagine residues. To determine whether this also holds for transmembrane β-strands, we calculated and statistically analyzed the twist and bend angles of four-residue frames of β-strands in both transmembrane and water-soluble β-barrel proteins with known three-dimensional structures. In the case of transmembrane β-strands, we found that twisting was suppressed even for frames not containing serine, threonine, or asparagine residues. The suppression of twisting in transmembrane β-strands could be attributed to the propagation of the suppressive effect of serine, threonine, and asparagine residues within a frame to the neighboring, hydrogen-bonded strands under the restriction that all strands in the closed barrel structure must have similar twist angles. A similar tendency was also observed for water-soluble β-barrel proteins. We previously showed that the dominant driving force for β-strand bending is hydrophobic interactions involving aromatic residues within and outside the strand. Transmembrane β-barrels have no hydrophobic core; however, rather hydrophilic residues predominate inside the barrel or the β-strands of transmembrane β-barrels have larger bend angles than those of water-soluble β-barrels. Our results reveal that, in transmembrane β-barrel proteins, the glycine-aromatic ring motif is important for generating the β-strand bending necessary for barrel formation.

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“…The positive or negative sign of the local bend angle is the sign of the scalar product between the cross product

\overset{LM}{true} \times \overset{MN}{true}

and the perpendicular vector

\overset{{RC}_{α} ((), i + 1)}{true}

N^{'} = \frac{N}{sin (()||, {normalθ}^{bend})}

…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

β‐Strand twisting/bending in soluble and transmembrane β‐barrel structures

2018

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“…1B). We relied on sidechain packing to drive strand bending in strands without β-bulges (see ref (26) and fig. S5).…”

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confidence: 99%

Principles for designing proteins with cavities formed by curved β sheets

Marcos

Basanta

Chidyausiku

et al. 2017

Science

123

125

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Active sites and ligand binding cavities in native proteins are often formed by curved β-sheets, and the ability to control β-sheet curvature would allow design of binding proteins with cavities customized to specific ligands. Towards this end, we investigated the mechanisms controlling β-sheet curvature by studying the geometry of β-sheets in naturally occurring protein structures and * Correspondence to: dabaker@u.washington.edu. † These authors contributed equally to this work. Supplementary Materials: Materials and MethodsFigs. S1 to S22 Tables S1 to S7 Input files and command lines for design calculations HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript folding simulations. The principles emerging from this analysis were used to de novo design a series of proteins with curved β-sheets topped with a-helices. NMR and crystal structures of the designs closely match the computational models, showing that β-sheet curvature can be controlled with atomic-level accuracy. Our approach enables the design of proteins with cavities and provides a route to custom design ligand binding and catalytic sites.Ligand binding proteins with curved β-sheets surrounding the binding pocket, as in the NTF2-like, β-barrel, and jelly roll folds, play key roles in molecular recognition, metabolic pathways and cell signaling. Approaches to designing small molecule binding proteins and enzymes to date have started by searching for native protein scaffolds with ligand binding pockets with roughly the right geometry, and then redesigning the surrounding residues to optimize interactions with the small molecule. While this approach has yielded new binding proteins and catalysts (1-5), it is not optimal: there may be no naturally occurring scaffold with a pocket with the correct geometry, and introduction of mutations in the design process may change the pocket structure (6, 7). Building de novo proteins with custom-tailored binding sites could be a more effective strategy, but this remains an outstanding challenge (8-11). De novo protein design has recently focused on proteins with ideal backbone structures (12-16) (straight helices, uniform β-strands and short loops; see ref (17) for a recent exception) and optimal core sidechain packing, but the binding pockets of naturally occurring proteins lie on concave surfaces formed by non-ideal features such as kinked helices, curved β-sheets or long loops. The design of proteins with concave surfaces requires examination of how such irregular structural features can be programmed into the amino acid sequence.We begin by analyzing how classic (18, 19) β-bulges (irregularities in the pleating of edge strands) and register shifts (local termination of strand pairing) coupled with intrinsic β-strand geometry induce curvature in antiparallel β-sheets (20, 21). We quantify the curvature of an edge strand making an antiparallel pairing with a second strand by the bend angle (Fig. 1A). The absolute value of the bend angle (α) at residue i is the angle bet...

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“…The destabilizing effect of V228 is not surprising. Indeed, from the propensity of the different amino-acids for a-helix or b-strand, 47 Valine does not favor a-helix formation. Furthermore, in M228V CpxA, two successive Valines are located at the positions 228 and 229, and molecular dynamics trajectories recorded on an a helix containing two successive Valines have shown 48 a larger drift of the a carbon coordinates and a decrease of the hydrogen bonds formation.…”

Section: Discussionmentioning

confidence: 99%

Modification in hydrophobic packing of HAMP domain induces a destabilization of the auto‐phosphorylation site in the histidine kinase CpxA

et al. 2016

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The histidine kinases belong to the family of two-component systems, which serves in bacteria to couple environmental stimuli to adaptive responses. Most of the histidine kinases are homodimers, in which the HAMP and DHp domains assemble into an elongated helical region flanked by two CA domains. Recently, X-ray crystallographic structures of the cytoplasmic region of the Escherichia coli histidine kinase CpxA were determined and a phosphotransferase-defective mutant, M228V, located in HAMP, was identified. In the present study, we recorded 1 μs molecular dynamics trajectories to compare the behavior of the WT and M228V protein dimers. The M228V modification locally induces the appearance of larger voids within HAMP as well as a perturbation of the number of voids within DHp, thus destabilizing the HAMP and DHp hydrophobic packing. In addition, a disruption of the stacking interaction between F403 located in the lid of the CA domain involved in the auto-phosphorylation and R296 located in the interacting DHp region, is more often observed in the presence of the M228V modification. Experimental modifications R296A and R296D of CpxA have been observed to reduce also the CpxA activity. These observations agree with the destabilization of the R296/F403 stacking, and could be the sign of the transmission of a conformational event taking place in HAMP to the auto-phosphorylation site of histidine kinase. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 670-682, 2016.

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The origin of β-strand bending in globular proteins

Cited by 18 publications

References 27 publications

β‐Strand twisting/bending in soluble and transmembrane β‐barrel structures

β‐Strand twisting/bending in soluble and transmembrane β‐barrel structures

Principles for designing proteins with cavities formed by curved β sheets

Modification in hydrophobic packing of HAMP domain induces a destabilization of the auto‐phosphorylation site in the histidine kinase CpxA

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