Designability landscape reveals sequence features that define axial helix rotation in four-helical homo-oligomeric antiparallel coiled-coil structures

Szczepaniak, Krzysztof; Łach, Grzegorz; Bujnicki, Janusz M.; Dunin-Horkawicz, Stanisław

doi:10.1016/j.jsb.2014.09.007

Cited by 15 publications

(16 citation statements)

References 33 publications

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“…4a). The large Leu side chain apparently disrupts the cross-α packing, and instead defaults to form a canonical antiparallel four-helix coiled coil 24 (Fig. 4b).…”

Section: Resultsmentioning

confidence: 99%

Designed peptides that assemble into cross-α amyloid-like structures

Zhang

Huang²,

Yang

et al. 2018

Nat Chem Biol

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Amyloids adopt 'cross-β' structures composed of long, twisted fibrils with β-strands running perpendicular to the fibril axis. Recently, a toxic peptide was proposed to form amyloid-like cross-α structures in solution, with a planar bilayer-like assembly observed in the crystal structure. Here we crystallographically characterize designed peptides that assemble into spiraling cross-α amyloid-like structures, which resemble twisted β-amyloid fibrils. The peptides form helical dimers, stabilized by packing of small and apolar residues, and the dimers further assemble into cross-α amyloid-like fibrils with superhelical pitches ranging from 170 Å to 200 Å. When a small residue that appeared critical for packing was converted to leucine, it resulted in structural rearrangement to a helical polymer. Fluorescently tagged versions of the designed peptides form puncta in mammalian cells, which recover from photobleaching with markedly different kinetics. These structural folds could be potentially useful for directing in vivo protein assemblies with predetermined spacing and stabilities.

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“…4a). The large Leu side chain apparently disrupts the cross-α packing, and instead defaults to form a canonical antiparallel four-helix coiled coil 24 (Fig. 4b).…”

Section: Resultsmentioning

confidence: 99%

Designed peptides that assemble into cross-α amyloid-like structures

Zhang

Huang²,

Yang

et al. 2018

Nat Chem Biol

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“…We have also analyzed the two crystal structures using the SamCC-Turbo server tool . The apo- GR CSL16CL23C structure shows 3SCC radius, periodicity, and axial helical rotation (defined in ref ) very similar to those of ORF1pCCD (Figure S2), especially in the modeled region that includes the dual Cys 3 a -site layers. This supports our prediction that the designed peptide is a good structural model of the ORF1pCCD Cys 3 a -site layers, and that their metal binding properties should be highly similar.…”

Section: Discussionmentioning

confidence: 99%

Open Reading Frame 1 Protein of the Human Long Interspersed Nuclear Element 1 Retrotransposon Binds Multiple Equivalents of Lead

et al. 2021

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The human long interspersed nuclear element 1 (LINE1) has been implicated in numerous diseases and has been suggested to play a significant role in genetic evolution. Open reading frame 1 protein (ORF1p) is one of the two proteins encoded in this self-replicating mobile genetic element, both of which are essential for retrotransposition. The structure of the three-stranded coiled-coil domain of ORF1p was recently solved and showed the presence of tris-cysteine layers in the interior of the coiled-coil that could function as metal binding sites. Here, we demonstrate that ORF1p binds Pb(II). We designed a model peptide, GRCSL16CL23C, to mimic two of the ORF1p Cys3 layers and crystallized the peptide both as the apo-form and in the presence of Pb(II). Structural comparison of the ORF1p with apo-(GRCSL16CL23C)3 shows very similar Cys3 layers, preorganized for Pb(II) binding. We propose that exposure to heavy metals, such as lead, could influence directly the structural parameters of ORF1p and thus impact the overall LINE1 retrotransposition frequency, directly relating heavy metal exposure to genetic modification.

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“…Measurements of Crick angles in experimentally determined structures using SamCC showed that coiled coils rarely assume an ideal x-da packing, in which helices are rotated by +26° or −26°. Rather, a continuum of axial rotational states was observed, predominantly in coiled coils with a-d-e cores (Dunin-Horkawicz and Lupas 2010a); in contrast, coiled coils with a-d-g cores are rarely observed and their rotation angles are typically <10° (Szczepaniak et al 2014). A survey of natural and computed structures found that small hydrophobic residues in position e and hydrophilic residues in position g favour a-d-e cores; the opposite distribution favours a-d-g cores (Dunin-Horkawicz and Lupas 2010b; Szczepaniak et al 2014).…”

Section: Coiled Coils With Variant Core Geometrymentioning

confidence: 99%

“…Rather, a continuum of axial rotational states was observed, predominantly in coiled coils with a-d-e cores (Dunin-Horkawicz and Lupas 2010a); in contrast, coiled coils with a-d-g cores are rarely observed and their rotation angles are typically <10° (Szczepaniak et al 2014). A survey of natural and computed structures found that small hydrophobic residues in position e and hydrophilic residues in position g favour a-d-e cores; the opposite distribution favours a-d-g cores (Dunin-Horkawicz and Lupas 2010b; Szczepaniak et al 2014). Depending on the sidechain size of the residues co-opted into the core (e in the case of a-d-e cores, g for a-d-g cores) the cross-sections of the resulting bundles may range from square (e.g.…”

Section: Coiled Coils With Variant Core Geometrymentioning

confidence: 99%

“…Although some coiled coils with x-da packing resemble Alacoils in having a seam of small residues that leads to close, pairwise association of their helices, the two packing modes differ fundamentally in the axial rotation state of their helices with respect to the bundle. Whereas helices showing Alacoil interactions are essentially unrotated (Dunin-Horkawicz and Lupas 2010a), helices with x-da interactions are rotated by > ±10° with respect to the bundle axis (Szczepaniak et al 2014). An example is provided by the four-helical bundle formed by the Lac repressor tetramer, Lac21, which was described as a ferritin-like Alacoil (Solan et al 2002), but, in fact, shows complementary x-da packing with an a-d-e core, due to the ~16° counter-clockwise rotation of its helices (Table 4.1).…”

Section: Coiled Coils With Variant Core Geometrymentioning

confidence: 99%

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The Structure and Topology of α-Helical Coiled Coils

Lupas

Baßler

Dunin-Horkawicz

2017

Subcellular Biochemistry

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α-Helical coiled coils constitute one of the most diverse folds yet described. They range in length over two orders of magnitude; they form rods, segmented ropes, barrels, funnels, sheets, spirals, and rings, which encompass anywhere from two to more than 20 helices in parallel or antiparallel orientation; they assume different helix crossing angles, degrees of supercoiling, and packing geometries. This structural diversity supports a wide range of biological functions, allowing them to form mechanically rigid structures, provide levers for molecular motors, project domains across large distances, mediate oligomerization, transduce conformational changes and facilitate the transport of other molecules. Unlike almost any other protein fold known to us, their structure can be computed from parametric equations, making them an ideal model system for rational protein design. Here we outline the principles by which coiled coils are structured, review the determinants of their folding and stability, and present an overview of their diverse architectures.

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Designability landscape reveals sequence features that define axial helix rotation in four-helical homo-oligomeric antiparallel coiled-coil structures

Cited by 15 publications

References 33 publications

Designed peptides that assemble into cross-α amyloid-like structures

Designed peptides that assemble into cross-α amyloid-like structures

Open Reading Frame 1 Protein of the Human Long Interspersed Nuclear Element 1 Retrotransposon Binds Multiple Equivalents of Lead

The Structure and Topology of α-Helical Coiled Coils

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