Crystal Structure of a Synthetic Triple-Stranded α-Helical Bundle

Lovejoy, Brett; Choe, Seunghyon; Cascio, Duilio; McRorie, Donald K.; DeGrado, William F.; Eisenberg, David

doi:10.1126/science.8446897

Cited by 297 publications

(251 citation statements)

References 40 publications

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“…ture of peptide LZ is in agreement with the crystal structure of peptide "coil-Ser" whose sequence is identical with that of LZ, except for Trp at position 2 and Ser at position 14 (Lovejoy et al, 1993). Increasing ACS destabilized the noncovalent interaction in the coiled-coil complexes.…”

Section: Identification Of Two-and Three-stranded Coiled Coilssupporting

confidence: 82%

“…Several model leucine zippers based on the sequences of naturally occurring coiled coils have been designed (Hodges et al, 1988;O'Neil & DeGrado, 1990;Engel et al, 1991;Cohen & Parry, 1994). One such model, named "coil-Ser," has been crystallized recently and shown to form a three-stranded coiled coil (Lovejoy et al, 1993). In the crystal of this and other leucine zippers, hydrophobic interactions between the a-helical polypeptide chains are a dominant stabilizing force.…”

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confidence: 99%

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Characterization of leucine zipper complexes by electrospray ionization mass spectrometry

et al. 1995

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The development of "soft" ionization methods has enabled the mass spectrometric analysis of higher-order structural features of proteins. We have applied electrospray ionization mass spectrometry (ESI-MS) to the analysis of the number and composition of polypeptide chains in homomeric and heteromeric leucine zippers. In comparison with other methods that have been used to analyze leucine zippers, such as analytical ultracentrifugation, gel chromatography, or electrophoretic band shift assays, ESI-MS is very fast and highly sensitive and provides a straightforward way to distinguish between homomeric and heteromeric coiled-coil structures. ESI-MS analyses were carried out on the parallel dimeric leucine zipper domain GCNCpl of the yeast transcription factor GCN4 and on three synthetic peptides with the sequences Ac-EYEALEKKLAAX,EAKX,QALEKKLEALEHC-amide:peptide LZ ( X , , X2 = Leu), peptide LZ(12A) (X, = Ala, X2 = Leu), and peptide LZ(16N) (X, = Leu, X2 = Asn). Equilibrium ultracentrifugation analysis showed that LZ forms a trimeric coiled coil and this could be confirmed unequivocally by ESI-MS as could the dimeric nature of GCN4-p1. The formation of heteromeric two-and threestranded leucine zippers composed of chains from LZ and LZ(12A), or from GCNCpl and LZ, was demonstrated by ESI-MS and confirmed by fluorescence quenching experiments on fluorescein-labeled peptides. The results illustrate the adaptability and flexibility of the leucine zipper motif, properties that could be useful to the design of specific protein assemblies by way of coiled-coil domains.

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Section: Identification Of Two-and Three-stranded Coiled Coilssupporting

confidence: 82%

mentioning

confidence: 99%

Characterization of leucine zipper complexes by electrospray ionization mass spectrometry

et al. 1995

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“…The results indicate the average relative CAT conversion + 1 standard error Although Mmip1 lacks a DNA binding domain, its ZIP domain is nevertheless structurally reminiscent of the ZIP domains of proteins such as c-fos, c-jun, and GCN4. In these cases, the`a' and`d' positions of the heptad repeats tend to be comprised of hydrophobic residues (Lovejoy et al, 1993;Zhu et al, 1993). This is indeed the case in Mmip1 where seven of nine such residues are hydrophobic compared with eight of nine in the case of GCN4 and c-jun and six of ten in the case of c-fos.…”

Section: Endogenous Mmip1 Expression and Co-immunoprecipitation With mentioning

confidence: 91%

Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc

et al. 1998

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C-myc, a member of the basic helix ± loop ± helix ± leucine zipper (bHLH-ZIP) protein family activates target genes in heterodimeric association with another bHLH-ZIP protein, Max. Max readily homodimerizes, competes with C-myc-Max heterodimers, and represses transcription. Four additional bHLH-ZIP proteins, Mad1, Mxi1, Mad3 and Mad4, heterodimerize with Max and also repress transcription of c-myc-responsive genes. We employed a yeast two-hybid approach to identify proteins which interact with Mxi. We identi®ed a novel ZIP-containing protein, Mmip1 (Mad memberinteracting protein 1) that strongly dimerizes with all four Mad members, but not with c-myc, Max, or with unrelated HLH proteins. The Mmip1-Mxi association is mediated by the ZIP domain of each polypeptide and is as strong or stronger than the associations between cmyc and Max or Max and Mxi1. In vitro, Mmip1 can inhibit DNA binding by Max-Mad heterodimers and, in vivo, can reverse the suppressive e ects of Mad proteins on c-myc functions. Mmip1 is found in a variety of cells types, is induced by serum stimulation, and can be coimmunoprecipitated from ®broblasts in association with Mxi1. By interfering with the dimerization between Max and Mad family member proteins, Mmip1 can indirectly up-regulate the transcriptional activity of c-myc and suppress the antiproliferative actions of Mad proteins.

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“…With the addition of the acetyl cap, our coiled-coil model shifts the numbering scheme by þ1 compared with the PDB version. PDB code 1COS 22 contains four heptads similar to (LaEbAcLdEeGfKg) n . It was originally designed to mimic the structural features of the tropomyosin coiled-coil dimer.…”

Section: Model Systemsmentioning

confidence: 99%

“…Coil-Ser was a synthetic peptide designed to form a parallel coiled-coil dimer, but crystallization showed it to be an antiparallel trimer. 22 This was attributed primarily to hydrophobic interactions and possibly to helix macrodipole interactions, rotamer energies, and steric effects.…”

Section: Introductionmentioning

confidence: 99%

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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Crystal Structure of a Synthetic Triple-Stranded α-Helical Bundle

Cited by 297 publications

References 40 publications

Characterization of leucine zipper complexes by electrospray ionization mass spectrometry

Characterization of leucine zipper complexes by electrospray ionization mass spectrometry

Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc

Computational analysis of residue contributions to coiled‐coil topology

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