Peptide ‘Velcro’: Design of a heterodimeric coiled coil

O’Shea, Erin K.; Lumb, Kevin J.; Kim, Peter

doi:10.1016/0960-9822(93)90063-t

Cited by 437 publications

(514 citation statements)

References 37 publications

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“…The primary structure of coiled-coil structures is characterized by heptads of residues, (abcdefg) n , with a unique pattern of internal a and d positions occupied mostly by apolar residues forming an hydrophobic core and positions g and e occupied by charged residues. The hydrophobic core of coiled coils is important for protein-protein interactions with a matching α-helix and mutagenesis of these positions affects the stability of this interaction [32]. It is important to note that the presence of charged residues at the core positions of coiled coils are correlated with proper alignment, orientation and selectivity of coiled-coils and contribute considerably to their stability [9,32].…”

Section: Role Of Coiled Coil Structures In Oligomerization Of Differementioning

confidence: 99%

The pre-pore from Bacillus thuringiensis Cry1Ab toxin is necessary to induce insect death in Manduca sexta

et al. 2008

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The insecticidal Cry toxins from Bacillus thuringiensis bacteria are pore-forming toxins that lyse midgut epithelial cells in insects. We have previously proposed that they form pre-pore oligomeric intermediates before membrane insertion.For formation of these oligomers coiled-coil structures are important, and helix α-3 from Cry toxins could form coiled-coils. Our data shows that different mutations in helix α-3 are affected in pore formation and toxicity. Mutants affected in toxicity bind Bt-R 1 receptor with a similar K D as the wild type toxin but do not form oligomers nor induce pore formation in planar lipid bilayers, indicating that the pre-pore oligomer is an obligate intermediate in the intoxication of Cry1Ab toxin and that interaction of monomeric Cry1Ab with Bt-R 1 is not enough to kill susceptible larvae.

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Section: Role Of Coiled Coil Structures In Oligomerization Of Differementioning

confidence: 99%

The pre-pore from Bacillus thuringiensis Cry1Ab toxin is necessary to induce insect death in Manduca sexta

et al. 2008

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“…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. Similarly,`e' and`g' residues tend to be comprised of hydrophobic amino acids (O'Shea et al, 1993;Vinson et al, 1993). At these positions, four of the eight e + g residues in Mmip1 are charged versus ®ve of eight in GCN4, and six of ten each in c-jun and c-fos.…”

Section: Endogenous Mmip1 Expression and Co-immunoprecipitation With mentioning

confidence: 99%

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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“…2,16,18,19 This is also exploited in coiled-coil design: judicious placement of complementary charges-e.g., Lys-Glu pairs at e and g-can be used to pattern sequences to control homotypic or heterotypic assembly of peptides otherwise possessing the same core a & d residues. [19][20][21][22] Together, such heuristics have been used to design a suite of coiled-coil components, 8,[23][24][25] which have been used as modular building blocks in various synthetic-biology applications. [26][27][28][29][30] The above said, the a/d interfaces are not the exclusive province of hydrophobic residues; indeed, ≈1/4 of residues at these interfaces of structurally defined coiled coils are polar.…”

Section: Introductionmentioning

confidence: 99%

N@a and N@d: Oligomer and Partner Specification by Asparagine in Coiled-Coil Interfaces

Fletcher¹,

Bartlett²,

Boyle³

et al. 2017

ACS Chem. Biol.

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The α-helical coiled coil is one of the best-studied protein–protein interaction motifs. As a result, sequence-to-structure relationships are available for the prediction of natural coiled-coil sequences and the de novo design of new ones. However, coiled coils adopt a wide range of oligomeric states and topologies, and our understanding of the specification of these and the discrimination between them remains incomplete. Gaps in our knowledge assume more importance as coiled coils are used increasingly to construct biomimetic systems of higher complexity; for this, coiled-coil components need to be robust, orthogonal, and transferable between contexts. Here, we explore how the polar side chain asparagine (Asn, N) is tolerated within otherwise hydrophobic helix–helix interfaces of coiled coils. The long-held view is that Asn placed at certain sites of the coiled-coil sequence repeat selects one oligomer state over others, which is rationalized by the ability of the side chain to make hydrogen bonds, or interactions with chelated ions within the coiled-coil interior of the favored state. We test this with experiments on de novo peptide sequences traditionally considered as directing parallel dimers and trimers, and more widely through bioinformatics analysis of natural coiled-coil sequences and structures. We find that when located centrally, rather than near the termini of such coiled-coil sequences, Asn does exert the anticipated oligomer-specifying influence. However, outside of these bounds, Asn is observed less frequently in the natural sequences, and the synthetic peptides are hyperthermostable and lose oligomer-state specificity. These findings highlight that not all regions of coiled-coil repeat sequences are equivalent, and that care is needed when designing coiled-coil interfaces.

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Peptide ‘Velcro’: Design of a heterodimeric coiled coil

Cited by 437 publications

References 37 publications

The pre-pore from Bacillus thuringiensis Cry1Ab toxin is necessary to induce insect death in Manduca sexta

The pre-pore from Bacillus thuringiensis Cry1Ab toxin is necessary to induce insect death in Manduca sexta

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

N@a and N@d: Oligomer and Partner Specification by Asparagine in Coiled-Coil Interfaces

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