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

2006 ◽  
Vol 155 (2) ◽  
pp. 146-153 ◽  
Author(s):  
Richard A. Kammerer ◽  
Michel O. Steinmetz
Keyword(s):  
De Novo ◽  
Peptides ◽  
1994 ◽  
pp. 1060-1062
Author(s):  
D. G. Myszka ◽  
I. M. Chaiken
Keyword(s):  
De Novo ◽  

1996 ◽  
Vol 74 (2) ◽  
pp. 133-154 ◽  
Author(s):  
Robert S. Hodges

The two-stranded α-helical coiled-coil is a universal dimerization domain used by nature in a diverse group of proteins. The simplicity of the coiled-coil structure makes it an ideal model system to use in understanding the fundamentals of protein folding and stability and in testing the principles of de novo design. The issues that must be addressed in the de novo design of coiled-coils for use in research and medical applications are (i) controlling parallel versus antiparallel orientation of the polypeptide chains, (ii) controlling the number of helical strands in the assembly (iii) maximizing stability of homodimers or heterodimers in the shortest possible chain length that may require the engineering of covalent constraints, and (iv) the ability to have selective heterodimerization without homodimerization, which requires a balancing of selectivity versus affinity of the dimerization strands. Examples of our initial inroads in using this de novo design motif in various applications include: heterodimer technology for the detection and purification of recombinant peptides and proteins; a universal dimerization domain for biosensors; a two-stage targeting and delivery system; and coiled-coils as templates for combinatorial helical libraries for basic research and drug discovery and as synthetic carrier molecules. The universality of this dimerization motif in nature suggests an endless number of possibilities for its use in de novo design, limited only by the creativity of peptide–protein engineers.Key words: de novo design of proteins, α-helical coiled-coils, protein folding, protein stability, dimerization domain, dimerization motif.


2015 ◽  
Vol 6 (11) ◽  
pp. 6505-6509 ◽  
Author(s):  
Chao Wang ◽  
Wenqing Lai ◽  
Fei Yu ◽  
Tianhong Zhang ◽  
Lu Lu ◽  
...  

Isopeptide bridge-tethered ultra-stable coiled-coil trimers have been de novo designed as structure-directing auxiliaries to guide HIV-1 gp41 NHR-peptide trimerization.


2021 ◽  
Author(s):  
William M. Dawson ◽  
Freddie J.O. Martin ◽  
Guto G. Rhys ◽  
Kathryn L. Shelley ◽  
R. Leo Brady ◽  
...  

ABSTRACTThe rational design of linear peptides that assemble controllably and predictably in water is challenging. Sequences must encode unique target structures and avoid alternative states. However, the stabilizing and discriminating non-covalent forces available are weak in water. Nonetheless, for α-helical coiled-coil assemblies considerable progress has been made in rational de novo design. In these, sequence repeats of nominally hydrophobic (h) and polar (p) residues, hpphppp, direct the assembly of amphipathic helices into dimeric to tetrameric bundles. Expanding this pattern to hpphhph can produce larger α-helical barrels. Here, we show that pentamers to nonamers are achieved simply by varying the residue at one of these h sites. In L/I-K-E-I-A-x-Z repeats, decreasing the size of Z from threonine to serine to alanine to glycine gives progressively larger oligomers. X-ray crystal structures of the resulting α-helical barrels rationalize this: side chains at Z point directly into the helical interfaces, and smaller residues allow closer helix contacts and larger assemblies.


2008 ◽  
Vol 45 (1) ◽  
pp. 106-116 ◽  
Author(s):  
Jianing Wang ◽  
Jiannan Feng ◽  
Ming Shi ◽  
Lu Qian ◽  
Liyong Chen ◽  
...  

2010 ◽  
Vol 17 (2) ◽  
pp. 100-106 ◽  
Author(s):  
Helena Gradišar ◽  
Roman Jerala
Keyword(s):  
De Novo ◽  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fabio Lapenta ◽  
Jana Aupič ◽  
Marco Vezzoli ◽  
Žiga Strmšek ◽  
Stefano Da Vela ◽  
...  

AbstractCoiled-coil protein origami (CCPO) is a modular strategy for the de novo design of polypeptide nanostructures. CCPO folds are defined by the sequential order of concatenated orthogonal coiled-coil (CC) dimer-forming peptides, where a single-chain protein is programmed to fold into a polyhedral cage. Self-assembly of CC-based nanostructures from several chains, similarly as in DNA nanotechnology, could facilitate the design of more complex assemblies and the introduction of functionalities. Here, we show the design of a de novo triangular bipyramid fold comprising 18 CC-forming segments and define the strategy for the two-chain self-assembly of the bipyramidal cage from asymmetric and pseudo-symmetric pre-organised structural modules. In addition, by introducing a protease cleavage site and masking the interfacial CC-forming segments in the two-chain bipyramidal cage, we devise a proteolysis-mediated conformational switch. This strategy could be extended to other modular protein folds, facilitating the construction of dynamic multi-chain CC-based complexes.


2001 ◽  
Vol 8 (11) ◽  
pp. 1025-1032 ◽  
Author(s):  
S.A Potekhin ◽  
T.N Melnik ◽  
V Popov ◽  
N.F Lanina ◽  
A.A Vazina ◽  
...  
Keyword(s):  
De Novo ◽  

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