courses-img1News
9th Asian Conference on Civil, Material and Environmental Science The 4th Climate, Weather and Water Forum International Conference of the German Society for Plant Sciences Emerging concepts and Novel Mechanisms in Organ Fibrosis Workshop ECB-IBS 2024 Five Editors-in-Chief Featured in the List of "Highly Cited Prof. Yun Zhang, Scientific Advisory Board of /Cardiovascular Sci Prof. Junhong Bai, Editorial Board Member of /Hydroecology and En Five Editorial Board Members of /Photocatalysis: Research and Pot 5th Edition of Cardiology World Conference
Sign in Register Submit

Journals Article Details

Synthetic Biology and Engineering-logo
Submit to SBE
Review Open Access

Coiled Coils as Versatile Modules for Mammalian Cell Regulation

Synthetic Biology and Engineering. 2023, 1(1), 10006; https://doi.org/10.35534/sbe.2023.10006
Estera Merljak 1,2,†    Anja Golob-Urbanc 1,†    Tjaša Plaper 1,†    Roman Jerala 1 *   
1
Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia
2
Interdisciplinary Doctoral Study of Biomedicine, Medical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia
†
These authors contributed equally.
*
Authors to whom correspondence should be addressed.

Received: 30 Jan 2023    Accepted: 30 Mar 2023    Published: 06 Apr 2023   

Full-Text HTML Full-Text PDF Download PDF

Abstract

Synthetic biology is a rapidly growing field that allows us to better understand biological processes at the molecular level, and enables therapeutic interventions and biotechnological applications. One of the most powerful tools in synthetic biology is the small, customizable, and modular protein–protein interaction domains, which is used to regulate a wide variety of processes within mammalian cells. Here we review designed coiled coil dimers that represent a set of heterodimerization domains with many advantages. These dimers have been useful for directing the localization of selected proteins within cells, enhancing chemical or light-regulated transcription, creating fast proteolysis-based responsive systems and protein secretion, genome editing, and cell–cell interaction motifs. Additionally, we will discuss how these building blocks are used in diverse applications, such as CAR T cell regulation and genome editing. Finally, we will look at the potential for future advances in synthetic biology using these building modules.

Keywords

Mammalian cell regulation; Coiled coil dimers; Protein–protein interactions; Transcriptional regulation; Protease-based signaling

References

1.
Wenz MT, Bertazzon M, Sticht J, Aleksić S, Gjorgjevikj D, Freund C, et al. Target Recognition in Tandem WW Domains: Complex Structures for Parallel and Antiparallel Ligand Orientation in h-FBP21 Tandem WW. J. Chem. Inf. Model. 2022, 62, 6586–6601. [Google Scholar]
2.
Kurochkina N, Guha U. SH3 domains: Modules of protein–protein interactions. Biophys. Rev. 2013, 5, 29–39. [Google Scholar]
3.
Scheffzek K, Welti S. Pleckstrin homology (PH) like domains—Versatile modules in protein-protein interaction platforms. FEBS Lett. 2012, 586, 2662–2673. [Google Scholar]
4.
Haslam NJ, Shields DC. Peptide-Binding Domains: Are Limp Handshakes Safest? Sci. Signal. 2012, 5, pe40. [Google Scholar]
5.
Crooks RO, Lathbridge A, Panek AS, Mason JM. Computational Prediction and Design for Creating Iteratively Larger Heterospecific Coiled Coil Sets. Biochemistry 2017, 56, 1573–1584. [Google Scholar]
6.
Lee H-J, Zheng JJ. PDZ domains and their binding partners: structure, specificity, and modification.  Cell Commun. Signal 2010, 8, 8. [Google Scholar]
7.
Ausländer S, Fussenegger M. Engineering Gene Circuits for Mammalian Cell–Based Applications. Cold Spring Harb. Perspect. Biol. 2016, 8, a023895. [Google Scholar]
8.
Kojima R, Fussenegger M. Synthetic Biology: Engineering Mammalian Cells To Control Cell‐to‐Cell Communication at Will. ChemBioChem 2019, 20, 994–1002. [Google Scholar]
9.
Crick FHC. The packing of α-helices: Simple coiled-coils. Acta Crystallogr. 1953, 6, 689–697. [Google Scholar]
10.
Lupas AN, Gruber M. The Structure of α-Helical Coiled Coils. In Advances in Protein Chemistry; Elsevier: Oxford, UK, 2005; Volume 70, pp. 37–38.
11.
Mason JM, Arndt KM. Coiled Coil Domains: Stability, Specificity, and Biological Implications. ChemBioChem 2004, 5, 170–176. [Google Scholar]
12.
Moutevelis E, Woolfson DN. A Periodic Table of Coiled-Coil Protein Structures. J. Mol. Biol. 2009, 385, 726–732. [Google Scholar]
13.
Burkhard P, Meier M, Lustig A. Design of a minimal protein oligomerization domain by a structural approach. Protein Sci. 2000, 9, 2294–2301. [Google Scholar]
14.
Kohn WD, Mant CT, Hodges RS. α-Helical Protein Assembly Motifs. J. Biol. Chem. 1997, 272, 2583–2586. [Google Scholar]
15.
Negron C, Keating AE. A Set of Computationally Designed Orthogonal Antiparallel Homodimers that Expands the Synthetic Coiled-Coil Toolkit. J. Am. Chem. Soc. 2014, 136, 16544–16556. [Google Scholar]
16.
Gradišar H, Jerala R. De novo design of orthogonal peptide pairs forming parallel coiled-coil heterodimers. J. Pept. Sci. 2011, 17, 100–106. [Google Scholar]
17.
Taylor WR, Chelliah V, Hollup SM, MacDonald JT, Jonassen I. Probing the “Dark Matter” of Protein Fold Space. Structure 2009, 17, 1244–1252. [Google Scholar]
18.
Ljubetič A, Lapenta F, Gradišar H, Drobnak I, Aupič J, Strmšek Ž, et al. Design of coiled-coil protein-origami cages that self-assemble in vitro and in vivo. Nat. Biotechnol. 2017, 35, 1094–1101. [Google Scholar]
19.
Shekhawat SS, Porter JR, Sriprasad A, Ghosh I. An Autoinhibited Coiled-Coil Design Strategy for Split-Protein Protease Sensors. J. Am. Chem. Soc. 2009, 131, 15284–15290. [Google Scholar]
20.
Lebar T, Lainšček D, Merljak E, Aupič J, Jerala R. A tunable orthogonal coiled-coil interaction toolbox for engineering mammalian cells. Nat. Chem. Biol. 2020, 16, 513–519. [Google Scholar]
21.
Drobnak I, Gradišar H, Ljubetič A, Merljak E, Jerala R. Modulation of Coiled-Coil Dimer Stability through Surface Residues while Preserving Pairing Specificity. J. Am. Chem. Soc. 2017, 139, 8229–8236. [Google Scholar]
22.
Plaper T, Aupič J, Dekleva P, Lapenta F, Keber MM, Jerala R, et al. Coiled-coil heterodimers with increased stability for cellular regulation and sensing SARS-CoV-2 spike protein-mediated cell fusion. Sci. Rep. 2021, 11, 9136. [Google Scholar]
23.
Newman JRS, Keating AE. Comprehensive Identification of Human bZIP Interactions with Coiled-Coil Arrays. Science 2003, 300, 2097–2101. [Google Scholar]
24.
Fink T, Lonzarić J, Praznik A, Plaper T, Merljak E, Leben K, et al. Design of fast proteolysis-based signaling and logic circuits in mammalian cells. Nat. Chem. Biol. 2019, 15, 115–122. [Google Scholar]
25.
Smith AJ, Thomas F, Shoemark D, Woolfson DN, Savery NJ. Guiding Biomolecular Interactions in Cells Using de Novo Protein–Protein Interfaces. ACS Synth. Biol. 2019, 8, 1284–1293. [Google Scholar]
26.
Thomas F, Boyle AL, Burton AJ, Woolfson DN. A Set of De Novo Designed Parallel Heterodimeric Coiled Coils with Quantified Dissociation Constants in the Micromolar to Sub-nanomolar Regime. J. Am. Chem. Soc. 2013, 135, 5161–5166. [Google Scholar]
27.
Edgell CL, Smith AJ, Beesley JL, Savery NJ, Woolfson DN. De Novo Designed Protein-Interaction Modules for In-Cell Applications. ACS Synth. Biol. 2020, 9, 427–436. [Google Scholar]
28.
Zhang F, Cong L, Lodato S, Kosuri S, Church GM, Arlotta P. Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription. Nat. Biotechnol. 2011, 29, 149–153. [Google Scholar]
29.
Geißler R, Scholze H, Hahn S, Streubel J, Bonas U, Behrens SE, et al. Transcriptional activators of human genes with programmable DNA-specificity. PLoS ONE 2011, 6, 1–7. [Google Scholar]
30.
Hall DB, Struhl K. The VP16 Activation Domain Interacts with Multiple Transcriptional Components as Determined by Protein-Protein Cross-linking in vivo. J. Biol. Chem. 2002, 277, 46043–46050. [Google Scholar]
31.
Sadowski I, Ma J, Triezenberg S, Ptashne M. GAL4-VP16 is an unusually potent transcriptional activator. Nature 1988, 335, 563–564. [Google Scholar]
32.
Perez-Pinera P, Kocak DD, Vockley CM, Adler AF, Kabadi AM, Polstein LR, et al. RNA-guided gene activation by CRISPR-Cas9–based transcription factors.  Nat. Methods 2013, 10, 973–976. [Google Scholar]
33.
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science 2012, 337, 816–821. [Google Scholar]
34.
Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, Arkin AP, et al. Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression. Cell 2013, 152, 1173–1183. [Google Scholar]
35.
Thakore PI, Black JB, Hilton IB, Gersbach CA. Editing the epigenome: technologies for programmable transcription and epigenetic modulation. Nat. Methods 2016, 13, 127–137. [Google Scholar]
36.
Chavez A, Tuttle M, Pruitt BW, Ewen-Campen B, Chari R, Ter-Ovanesyan D, et al. Comparison of Cas9 activators in multiple species. Nat. Methods 2016, 13, 563–567. [Google Scholar]
37.
Tanenbaum ME, Gilbert LA, Qi LS, Weissman JS, Vale RD. A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell 2014, 159, 635–646. [Google Scholar]
38.
Lainšček D, Forstnerič V, Mikolič V, Malenšek Š, Pečan P, Benčina M, et al. Coiled-coil heterodimer-based recruitment of an exonuclease to CRISPR/Cas for enhanced gene editing. Nat. Commun. 2022, 13, 3604. [Google Scholar]
39.
Golob-Urbanc A, Rajčević U, Strmšek Ž, Jerala R. Design of split superantigen fusion proteins for cancer immunotherapy. J. Biol. Chem. 2019, 294, 6294–6305. [Google Scholar]
40.
Praznik A, Fink T, Franko N, Lonzarić J, Benčina M, Jerala N, et al. Regulation of protein secretion through chemical regulation of endoplasmic reticulum retention signal cleavage. Nat. Commun. 2022, 13, 1323. [Google Scholar]
41.
Vlahos AE, Kang J, Aldrete CA, Zhu R, Chong LS, Elowitz MB, et al. Protease-controlled secretion and display of intercellular signals. Nat. Commun. 2022, 13, 912. [Google Scholar]
42.
Jazbec V, Jerala R, Benčina M. Proteolytically Activated CRAC Effectors through Designed Intramolecular Inhibition. ACS Synth. Biol. 2022, 11, 2756–2765. [Google Scholar]
43.
Honig B, Shapiro L. Adhesion Protein Structure, Molecular Affinities, and Principles of Cell-Cell Recognition. Cell 2020, 181, 520–535. [Google Scholar]
44.
Chao G, Wannier TM, Gutierrez C, Borders NC, Appleton E, Chadha A, et al. helixCAM: A platform for programmable cellular assembly in bacteria and human cells. Cell 2022, 185, 3551–3567.e39. [Google Scholar]
45.
Stevens AJ, Harris AR, Gerdts J, Kim KH, Trentesaux C, Ramirez JT, et al. Programming multicellular assembly with synthetic cell adhesion molecules. Nature 2023, 614, 144–152. [Google Scholar]
46.
FDA Approval Brings First Gene Therapy to the United States. Available online: https://www.fda.gov/news-events/press-announcements/fda-approval-brings-first-gene-therapy-united-states (accessed on 31 March 2023).
47.
Cho JH, Collins JJ, Wong WW. Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses. Cell 2018, 173, 1426–1438.e11. [Google Scholar]
48.
Cho JH, Okuma A, Sofjan K, Lee S, Collins JJ, Wong WW. Engineering advanced logic and distributed computing in human CAR immune cells. Nat. Commun. 2021, 12, 792. [Google Scholar]
49.
Li H-S, Wong NM, Tague E, Ngo JT, Khalil AS, Wong WW. High-performance multiplex drug-gated CAR circuits. Cancer Cell 2022, 40, 1294–1305.e4. [Google Scholar]
50.
Cordoba S, Onuoha S, Thomas S, Pignataro DS, Hough R, Ghorashian S, et al. CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: A phase 1 trial. Nat. Med. 2021, 27, 1797–1805. [Google Scholar]
51.
Gradišar H, Božič S, Doles T, Vengust D, Hafner-Bratkovič I, Mertelj A, et al. Design of a single-chain polypeptide tetrahedron assembled from coiled-coil segments. Nat. Chem. Biol. 2013, 9, 362–366. [Google Scholar]
52.
Clifford Boldridge W, Ljubetič A, Kim H, Lubock N, Szilágyi D, Lee J, et al. A Multiplexed Bacterial Two-Hybrid for Rapid Characterization of Protein–Protein Interactions and Iterative Protein Design. bioRxiv 2020. https://doi.org/10.1101/2020.11.12.377184.
Creative Commons

© 2024 by the authors; licensee SCIEPublish, SCISCAN co. Ltd. This article is an open access article distributed under the CC BY license (https://creativecommons.org/licenses/by/4.0/).