De novo design of a two-stranded coiled-coil switch peptide

Kammerer, Richard A.; Steinmetz, Michel O.

doi:10.1016/j.jsb.2006.01.017

Cited by 38 publications

(44 citation statements)

References 58 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1B). This denaturation profile, with a peculiarly low urea Cm, has often been encountered in denaturation studies of coiledcoil systems (8). Thermal denaturation curves, recorded at 222 nm, show that denaturation occurs in one step (data not shown).…”

Section: Methods (I) Cloning Expression and Purification Of Proteinsmentioning

confidence: 53%

See 1 more Smart Citation

Evidence for an Elongated Dimeric Structure of Heparin-Binding Hemagglutinin from Mycobacterium tuberculosis

et al. 2008

View full text Add to dashboard Cite

Heparin-binding hemagglutinin (HBHA) is a virulence factor of tuberculosis which is responsible for extrapulmonary dissemination of this disease. A thorough biochemical characterization of HBHA has provided experimental evidence of a coiled-coil nature of HBHA. These data, together with the low-resolution structures of a full-length form and a truncated form of HBHA obtained by small-angle X-ray scattering, have unambiguously indicated that HBHA has a dimeric structure with an elongated shape.

show abstract

Section: Methods (I) Cloning Expression and Purification Of Proteinsmentioning

confidence: 53%

“…1A). These spectra, with an ␣-helix band intensity at 208 nm stronger than that at 222 nm, are typical of proteins with a coiledcoil structure (1,8,12,25). To validate this result, we performed chemical denaturation, using urea as a denaturating agent, of HBHA⌬C.…”

Section: Methods (I) Cloning Expression and Purification Of Proteinsmentioning

confidence: 88%

Evidence for an Elongated Dimeric Structure of Heparin-Binding Hemagglutinin from Mycobacterium tuberculosis

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Supporting evidence for this conclusion is provided by Hodges and coworkers (48) who induced folding of a cortexillin/GCN4 hybrid lacking the canonical trigger sites by introducing stabilizing mutations that improved helicity without converting the sequence to the trigger consensus. Furthermore, we successfully demonstrated that a strategy employing networks of helix stabilizing interactions can be applied for the de novo design of uncommonly short and stable coiled coils (8,49), emphasizing that the knowledge gained in this study has potential for applications using coiledcoil domains.…”

Section: Discussionmentioning

confidence: 85%

Molecular basis of coiled-coil formation

Steinmetz

Jelesarov

Matousek

et al. 2007

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

Self Cite

125

129

View full text Add to dashboard Cite

Coiled coils have attracted considerable interest as design templates in a wide range of applications. Successful coiled-coil design strategies therefore require a detailed understanding of coiled-coil folding. One common feature shared by coiled coils is the presence of a short autonomous helical folding unit, termed ''trigger sequence,'' that is indispensable for folding. Detailed knowledge of trigger sequences at the molecular level is thus key to a general understanding of coiled-coil formation. Using a multidisciplinary approach, we identify and characterize here the molecular determinants that specify the helical conformation of the monomeric early folding intermediate of the GCN4 coiled coil. We demonstrate that a network of hydrogen-bonding and electrostatic interactions stabilize the trigger-sequence helix. This network is rearranged in the final dimeric coiled-coil structure, and its destabilization significantly slows down GCN4 leucine zipper folding. Our findings provide a general explanation for the molecular mechanism of coiled-coil formation.autonomous folding unit ͉ protein folding ͉ trigger sequence ͉ leucine zipper ͉ ␣-helix A lthough coiled coils have been used traditionally as model systems for protein folding studies, the molecular basis of how they fold is still largely unknown. A need for a detailed understanding of coiled-coil folding is relevant, particularly in light of the important functions these structures play in almost all biological processes, as well as the considerable attention coiled coils have recently garnered in a wide range of applications, including basic research, nanomaterials, protein engineering, biotechnology, and medicine (1-13). Furthermore, understanding the folding mechanisms of coiled coils is of fundamental interest to experimentalists and theoreticians challenged by the question of how the sequence of a protein defines its specific 3D structure. Along these lines, we have been interested particularly in coiled-coil ''trigger sequences,'' which encode stable monomeric ␣-helices that are indispensable for coiled-coil formation (14-18). Although there are a few examples of synthetic peptides that fold either into heterodimers (19) or at conditions of extremes of pH (20) without an apparent trigger sequence, the ''trigger site'' concept is generally accepted because these short autonomous helical folding units are structurally and functionally conserved in a large number of native coiled-coil proteins (reviewed in refs. 21-24). Detailed knowledge of the properties of trigger sequences at the molecular level is therefore key to an understanding of coiled-coil formation and function in general.The parallel two-stranded leucine zipper of the yeast transcriptional activator GCN4 is the best-characterized coiled coil and thus represents an excellent paradigm for a comprehensive analysis of the roles of trigger sequences in coiled-coil folding. Our current understanding of the folding kinetics of the GCN4 leucine zipper is based on extensive stopped-flow studies and te...

show abstract

“…A peptide with similar properties was designed by hand in 2005 [24], and both designs show solution properties consistent with the intended folds. Coiled-coil peptides have also been designed to form fibers (both amyloid and non-amyloid) upon external triggering by pH or temperature, or simply upon mixing [25][26][27][28].…”

Section: Novel Structures Switches and Functionsmentioning

confidence: 99%

Structural specificity in coiled-coil interactions

Grigoryan

Keating

2008

Current Opinion in Structural Biology

270

283

View full text Add to dashboard Cite

Coiled coils have a rich history in the field of protein design and engineering. Novel structures, such as the first 7-helix coiled coil, continue to provide surprises and insights. Large-scale data sets quantifying the influence of systematic mutations on coiled-coil stability are a valuable new asset to the area. Scoring methods based on sequence and/or structure can predict interaction preferences in coiled-coil-mediated bZIP transcription factor dimerization. Experimental and computational methods for dealing with the near-degeneracy of many coiled-coil structures appear promising for future design applications.

show abstract

De novo design of a two-stranded coiled-coil switch peptide

Cited by 38 publications

References 58 publications

Evidence for an Elongated Dimeric Structure of Heparin-Binding Hemagglutinin from Mycobacterium tuberculosis

Evidence for an Elongated Dimeric Structure of Heparin-Binding Hemagglutinin from Mycobacterium tuberculosis

Molecular basis of coiled-coil formation

Structural specificity in coiled-coil interactions

Contact Info

Product

Resources

About