Coiled Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution<sup>,</sup>

Yadav, Maneesh K.; Leman, Luke J.; Price, Daniel J.; Brooks, Charles L.; Stout, C.D.; Ghadiri, Mojtaba

doi:10.1021/bi060092q

Cited by 72 publications

(107 citation statements)

References 62 publications

(102 reference statements)

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“…The conformational flexibility of ␣-helical coiled-coils is a well-documented phenomenon (26,27), allowing for functionally relevant conformational heterogeneity and low interconversion energy barriers among alternate configurations. Our structural data of DesKC now provide strong evidence that the DHp domain is marginally stable and prone to rotational rearrangements in the context of the full-length protein.…”

Section: Discussionmentioning

confidence: 99%

Structural plasticity and catalysis regulation of a thermosensor histidine kinase

Albanesi

Martín

Trajtenberg

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

162

262

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Temperature sensing is essential for the survival of living cells. A major challenge is to understand how a biological thermometer processes thermal information to optimize cellular functions. Using structural and biochemical approaches, we show that the thermosensitive histidine kinase, DesK, from Bacillus subtilis is coldactivated through specific interhelical rearrangements in its central four-helix bundle domain. As revealed by the crystal structures of DesK in different functional states, the plasticity of this helical domain influences the catalytic activities of the protein, either by modifying the mobility of the ATP-binding domains for autokinase activity or by modulating binding of the cognate response regulator to sustain the phosphotransferase and phosphatase activities. The structural and biochemical data suggest a model in which the transmembrane sensor domain of DesK promotes these structural changes through conformational signals transmitted by the membrane-connecting two-helical coiled-coil, ultimately controlling the alternation between output autokinase and phosphatase activities. The structural comparison of the different DesK variants indicates that incoming signals can take the form of helix rotations and asymmetric helical bends similar to those reported for other sensing systems, suggesting that a similar switching mechanism could be operational in a wide range of sensor histidine kinases.coiled-coil ͉ conformational rearrangement ͉ crystallography ͉ signal transduction

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Section: Discussionmentioning

confidence: 99%

Structural plasticity and catalysis regulation of a thermosensor histidine kinase

Albanesi

Martín

Trajtenberg

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

162

262

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“…The lone pair would then be directed toward the C terminus. structures of homomeric assemblies with different aggregation states (42) and helix orientations (43).…”

Section: Discussionmentioning

confidence: 99%

Identifying important structural characteristics of arsenic resistance proteins by using designed three-stranded coiled coils

Touw

Nordman

Stuckey³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

154

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Arsenic, a contaminant of water supplies worldwide, is one of the most toxic inorganic ions. Despite arsenic's health impact, there is relatively little structural detail known about its interactions with proteins. Bacteria such as Escherichia coli have evolved arsenic resistance using the Ars operon that is regulated by ArsR, a repressor protein that dissociates from DNA when As(III) binds. This protein undergoes a critical conformational change upon binding As(III) with three cysteine residues. Unfortunately, structures of ArsR with or without As(III) have not been reported. Alternatively, de novo designed peptides can bind As(III) in an endo configuration within a thiolate-rich environment consistent with that proposed for both ArsR and ArsD. We report the structure of the As(III) complex of Coil Ser L9C to a 1.8-Å resolution, providing x-ray characterization of As(III) in a Tris thiolate protein environment and allowing a structural basis by which to understand arsenated ArsR.arsenic-binding proteins ͉ coiled coil peptides ͉ crystallography ͉ heavy metal toxicity ͉ protein design A rsenic toxicity is a worldwide problem as a natural contaminant of water supplies. Despite the fact that it is a human toxin and carcinogen, few structural reports on its interaction with biological ligands have appeared. Escherichia coli and other bacteria have evolved a detoxification mechanism that employs the arsRDABC operon (1). Arsenic removal by these encoded proteins is initiated when As(III) binds to ArsR, resulting in the dissociation of the repressor protein from the promoter DNA. The structure of the ArsA component of the ATP-dependent extrusion pump ArsAB with antimonite bound in close proximity to the nucleotide-binding site was able to provide some insight into the active transport of As(III) out of the cell (2). Additionally, structural characterization of substrate and product complexes of the arsenate reductase ArsC, which reduces arsenate (AsO 4 3Ϫ ) to arsenite (AsO 2 Ϫ ), has helped elucidate this step of the arsenic detoxification pathway (3, 4). Recent studies of E. coli ArsD indicate that it is a metallochaperone, transporting As(III) to ArsA for extrusion (5). Extended x-ray absorption fine structure and mutagenesis studies have shown that ArsR coordinates As(III) with three cysteine thiolates at a distance of 2.25 Å, a coordination mode that ArsD is also proposed to employ (1, 5). However, no x-ray or NMR structures of ArsR, the repressor protein, or ArsD have been reported to date. Furthermore, AsS 3 structures have not been reported for any biologically relevant small-molecule thiolates, such as glutathione, and only a handful of related AsS 3 complexes with aromatic ligands or chelated alkyl dithiolate coordination are reported (6).We set out to model the putative As(III) coordination environments of ArsR and ArsD in a designed peptide system. Previously, we have shown that the three-stranded coiled coildesigned with the heptad repeat strategy, such as TRI L16C (sequences of all peptides are in Table 1...

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“…Our model includes the full sequence. PDB code 1W5K 24 corresponds to a mutant of the GCN4-LI sequence (a parallel tetrameric coiled coil). The substitution of a single solvent-exposed glutamic acid residue (GLU20e to CYS) resulted in an antiparallel tetramer.…”

Section: Model Systemsmentioning

confidence: 99%

“…When compared with the parallel topology, side chain packing is much more efficient in the antiparallel coiled-coil tetramer. 24 The packing efficiency is more likely to make strong contributions when the side chains occupying the a and d positions are significantly different in size. Antiparallel coiled-coil tetramers such as the heterogeneous nuclear ribonucleoprotein (hnRNP) contain LEU, ILE, and VAL at the core positions, thus the packing effect will likely make only minor contributions in determining helix orientation.…”

Section: Introductionmentioning

confidence: 99%

“…25 A single substitution at a solvent-exposed site (GLU20eCYS) changed the topology of the tetrameric GCN4-LI peptide 5 from parallel to antiparallel. 24 An important structural feature in antiparallel coiled coils is the heptad register shift between neighboring helices. 26 Recent studies of antiparallel tetrameric coiled coils have identified at least five kinds of interaction patterns directed by hydrophobic repeats of a-d (1W5K), a-d-e (2R2V), and a-d-g (2B22) type.…”

Section: Introductionmentioning

confidence: 99%

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Computational analysis of residue contributions to coiled‐coil topology

Torre

Lazaridis

2011

Protein Science

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A variety of features are thought to contribute to the oligomeric and topological specificity of coiled coils. In previous work, we examined the determinants of oligomeric state. Here, we examine the energetic basis for the tendency of six coiled-coil peptides to align their a-helices in antiparallel orientation using molecular dynamics simulations with implicit solvation (EEF1.1). We also examine the effect of mutations known to disrupt the topology of these peptides. In agreement with experiment, ARG or LYS at a or d positions were found to stabilize the antiparallel configuration. The modeling suggests that this is not due to a-a 0 or d-d 0 repulsions but due to interactions with e 0 and g 0 residues. TRP at core positions also favors the antiparallel configuration. Residues that disfavor parallel dimers, such as ILE at d, are better tolerated in, and thus favor the antiparallel configuration. Salt bridge networks were found to be more stabilizing in the antiparallel configuration for geometric reasons: antiparallel helices point amino acid side chains in opposite directions. However, the structure with the largest number of salt bridges was not always the most stable, due to desolvation and configurational entropy contributions. In tetramers, the extent of stabilization of the antiparallel topology by core residues is influenced by the e 0 residue on a neighboring helix. Residues at b and c positions in some cases also contribute to stabilization of antiparallel tetramers. This work provides useful rules toward the goal of designing coiled coils with a well-defined and predictable three-dimensional structure.

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Coiled Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution^,

Cited by 72 publications

References 62 publications

Structural plasticity and catalysis regulation of a thermosensor histidine kinase

Structural plasticity and catalysis regulation of a thermosensor histidine kinase

Identifying important structural characteristics of arsenic resistance proteins by using designed three-stranded coiled coils

Computational analysis of residue contributions to coiled‐coil topology

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Coiled Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution,

Cited by 72 publications

References 62 publications

Structural plasticity and catalysis regulation of a thermosensor histidine kinase

Structural plasticity and catalysis regulation of a thermosensor histidine kinase

Identifying important structural characteristics of arsenic resistance proteins by using designed three-stranded coiled coils

Computational analysis of residue contributions to coiled‐coil topology

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Product

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Coiled Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution^,