Evaluation of de novo-designed coiled coils as off-the-shelf components for protein assembly

2017 ◽  
Vol 2 (2) ◽  
pp. 140-148 ◽  
Author(s):  
Ajitha S. Cristie-David ◽  
Aaron Sciore ◽  
Somayesadat Badieyan ◽  
Joseph D. Escheweiler ◽  
Philipp Koldewey ◽  
...  

Coiled coils are effective at oligomerizing larger proteins, but oligomerization states may change unless care is taken to optimize design.

2018 ◽  
Vol 9 (18) ◽  
pp. 4308-4316 ◽  
Author(s):  
Mike C. Groth ◽  
W. Mathis Rink ◽  
Nils F. Meyer ◽  
Franziska Thomas

Strand displacement in heterodimeric coiled coils follows a competitive binding mechanism and can be predicted by the ratio of KD values.


Author(s):  
Suyeong Han ◽  
Yongwon Jung

Nature uses a wide range of well-defined biomolecular assemblies in diverse cellular processes, where proteins are major building blocks for these supramolecular assemblies. Inspired by their natural counterparts, artificial protein-based assemblies have attracted strong interest as new bio-nanostructures, and strategies to construct ordered protein assemblies have been rapidly expanding. In this review, we provide an overview of very recent studies in the field of artificial protein assemblies, with the particular aim of introducing major assembly methods and unique features of these assemblies. Computational de novo designs were used to build various assemblies with artificial protein building blocks, which are unrelated to natural proteins. Small chemical ligands and metal ions have also been extensively used for strong and bio-orthogonal protein linking. Here, in addition to protein assemblies with well-defined sizes, protein oligomeric and array structures with rather undefined sizes (but with definite repeat protein assembly units) also will be discussed in the context of well-defined protein nanostructures. Lastly, we will introduce multiple examples showing how protein assemblies can be effectively used in various fields such as therapeutics and vaccine development. We believe that structures and functions of artificial protein assemblies will be continuously evolved, particularly according to specific application goals.


ChemBioChem ◽  
2017 ◽  
Vol 18 (19) ◽  
pp. 1888-1892 ◽  
Author(s):  
Somayesadat Badieyan ◽  
Aaron Sciore ◽  
Joseph D. Eschweiler ◽  
Philipp Koldewey ◽  
Ajitha S. Cristie-David ◽  
...  

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.


2016 ◽  
Vol 7 (3) ◽  
pp. 2207-2216 ◽  
Author(s):  
Matthew R. Berwick ◽  
Louise N. Slope ◽  
Caitlin F. Smith ◽  
Siobhan M. King ◽  
Sarah L. Newton ◽  
...  

Lanthanide binding site translation linearly along a coiled coil has a large impact on stability, coordination chemistry, and MRI relaxivity.


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