User:AzulRover/Coiled coil

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Copied from Coiled coil: A coiled coil is a structural motif in proteins in which 2–7[1] alpha-helices are coiled together like the strands of a rope. (Dimers and trimers are the most common types.) They have been found in roughly 5-10% of proteins and have a variety of functions.[2] They are one of the most widespread motifs found in protein-protein interactions. To aid protein study, several tools have been developed to predict coiled-coils in protein structures.[3] Many coiled coil-type proteins are involved in important biological functions, such as the regulation of gene expression — e.g., transcription factors. Notable examples are the oncoproteins c-Fos and c-Jun, as well as the muscle protein tropomyosin.

Article body[edit]

Functions[edit]

As coiled-coil domains are common among a significant amount of proteins in a wide variety of protein families, they help proteins fulfill various functions in the cell. Their primary feature is to facilitate protein-protein interaction and keep proteins or domains interlocked. This feature corresponds to several subfunctions, including membrane fusion, molecular spacing, oligomerization tags, vesicle movement, aid in movement proteins, cell structure, and more.[4]

Membrane fusion[edit]

Side view of the gp41 hexamer that initiates the entry of HIV into its target cell.

A coiled coil domain plays a role in HIV infection. Viral entry into CD4-positive cells commences when three subunits of a glycoprotein 120 (gp120) bind to CD4 receptor and a coreceptor.[5] Glycoprotein gp120 is closely associated with a trimer of gp41 via van der Waals interactions. Eventually, the gp41 N-terminal fusion peptide sequence anchors into the host cell. A spring-loaded mechanism is responsible for bringing the viral and cell membranes in close enough proximity that they will fuse. The origin of the spring-loaded mechanism lies within the exposed gp41, which contains two consecutive heptad repeats (HR1 and HR2) following the fusion peptide at the N terminus of the protein. HR1 forms a parallel, trimeric coiled coil onto which HR2 region coils, forming the trimer-of-hairpins (or six-helix bundle) structure, thereby facilitating membrane fusion through bringing the membranes close to each other.[6] The virus then enters the cell and begins its replication. Recently, inhibitors derived from HR2 such as Fuzeon (DP178, T-20) that bind to the HR1 region on gp41 have been developed.[7] However, peptides derived from HR1 have little viral inhibition efficacy due to the propensity for these peptides to aggregate in solution. Chimeras of these HR1-derived peptides with GCN4 leucine zippers have been developed and have shown to be more active than Fuzeon.[8]

The proteins SNAP-25, synaptobrevin, and syntaxin-1 have alpha-helices which interact with each other to form a coiled-coil SNARE complex. Zippering the domains together is believed to provide the necessary energy for vesicle fusion to occur.[9]

Molecular spacers[edit]

The coiled-coil motif may also act as a spacer between two objects within a cell. The lengths of these molecular spacer coiled-coil domains are highly conserved. The purpose of these molecular spacers may be to separate protein domains, thus keeping them from interacting, or to separate vesicles within the cell to mediate vesicle transport. An example of this first purpose is Omp‐α found in T. maritima.[10] Other proteins keep vesicles apart, such as p115, giantin, and GM130 which interact with each other via coiled-coil motifs and act as a tether between the Golgi and a nearby vesicle.[11] The family of proteins related to this activity of tethering vesicles to the Golgi are known as golgins.[12] Finally, there are several proteins with coiled-coil domains involved in the kinetochore, which keeps chromosomes separated during cell division. These proteins include Ndc-80, and Nuf2p. Related proteins interact with microtubules during cell division, of which mutation leads to cell death.[13]

Oligomerization tags[edit]

Because of their specific interaction coiled coils can be used as "tags" to stabilize or enforce a specific oligomerization state.[14] A coiled coil interaction has been observed to drive the oligomerization of the BBS2 and BBS7 subunits of the BBSome. [15] [16] Because coiled-coils generally interact with other coiled coils, they are found in proteins which are required to form dimers or tetramers with more copies of themselves.[17] Because of their ability in driving protein oligomerization, they have also been studied in their use in forming synthetic nanostructures.[18]

Biomedical Applications[edit]

Some examples of protein nanostructures made using coiled-coil motifs. The top three pictures shown in the figure more accurately models the nanostructure, while the pictures underneath describe their basic shape. These may be used as building blocks to create further nanostructures.[19]

Coiled-coil motifs have been experimented on as possible building block for nanostructures, in part because of their simple design and wide range of function based primarily on facilitating protein-protein interaction. Simple guidelines for de novo synthesis of new proteins containing coiled-coil domains have led to many applications being hypothesized, including drug delivery, regenerating tissue, protein origami, and much more.[20] In regards to drug delivery, coiled-coil domains would help overcome some of the hazards of chemotherapeutic drugs, by keeping them from leaking into healthy tissue as they are transported to their target. Coiled-coil domains can be made to bind to specific proteins or cell surface markers, allowing for more precise targeting in drug delivery.[21] Other functions would be to help store and transport drugs within the body that would otherwise degrade rapidly, by creating nanotubes and other structure svia the interlocking of coiled-coil motifs.[20] By utilizing the function of oligomerization of proteins via coiled-coil domains, antigen display can be amplified in vaccines, increasing their effectiveness.[22]

The oligomerization of coiled-coil motifs allows for the creation of protein origami and protein building blocks. Metal-ligand interactions, covalent bonds, and ionic interactions have been studied to manipulate possible coiled-coil interactions in this field of study.[20] Several different nanostructures can be made by combining coiled-coil motifs such that they are self-assembling building blocks. However, several difficulties remain with stability.[23] Using peptides with coiled-coil motifs for scaffolding has made it easier to create 3D structures for cell culturing. 3D hydrogels can be made with these peptides, and then cells may be loaded into the matrix.[24] This has applications in the study of tissue, tissue engineering, and more.[20]


Secondary and tertiary structure of the coiled-coil motif. The heptad repeat often consists of specific amino acids, seen in the figure. Knobs into packing is also shown.[19]

To be added to the "Design" section:

See also[edit]

Leucine zipper



Possible figures to use:

Leucine_zipper2GCN4_coiled_coil_dimer_1zik_rainbow


References[edit]

  1. ^ Liu J, Zheng Q, Deng Y, Cheng CS, Kallenbach NR, Lu M (Oct 2006). "A seven-helix coiled coil". Proceedings of the National Academy of Sciences of the United States of America. 103 (42): 15457–62. Bibcode:2006PNAS..10315457L. doi:10.1073/pnas.0604871103. PMC 1622844. PMID 17030805.
  2. ^ Szczepaniak, Krzysztof; Bukala, Adriana; da Silva Neto, Antonio Marinho; Ludwiczak, Jan; Dunin-Horkawicz, Stanislaw (2021-04-01). Elofsson, Arne (ed.). "A library of coiled-coil domains: from regular bundles to peculiar twists". Bioinformatics. 36 (22–23): 5368–5376. doi:10.1093/bioinformatics/btaa1041. ISSN 1367-4803. PMC 8016460. PMID 33325494.{{cite journal}}: CS1 maint: PMC format (link)
  3. ^ Walshaw, John; Woolfson, Derek N (2001-04-13). "SOCKET: a program for identifying and analysing coiled-coil motifs within protein structures11Edited by J. Thornton". Journal of Molecular Biology. 307 (5): 1427–1450. doi:10.1006/jmbi.2001.4545. ISSN 0022-2836.
  4. ^ Rose, Annkatrin; Schraegle, Shannon J.; Stahlberg, Eric A.; Meier, Iris (2005-11-16). "Coiled-coil protein composition of 22 proteomes – differences and common themes in subcellular infrastructure and traffic control". BMC Evolutionary Biology. 5 (1): 66. doi:10.1186/1471-2148-5-66. ISSN 1471-2148. PMC 1322226. PMID 16288662.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  5. ^ Shaik MM, Peng H, Lu J, Rits-Volloch S, Xu C, Liao M, Chen B (January 2019). "Structural basis of coreceptor recognition by HIV-1 envelope spike". Nature. 565 (7739): 318–323. doi:10.1038/s41586-018-0804-9. PMC 6391877. PMID 30542158.
  6. ^ Wilen CB, Tilton JC, Doms RW (August 2012). "HIV: cell binding and entry". Cold Spring Harbor Perspectives in Medicine. 2 (8): a006866. doi:10.1101/cshperspect.a006866. PMC 3405824. PMID 22908191.
  7. ^ Greenberg ML, Cammack N (August 2004). "Resistance to enfuvirtide, the first HIV fusion inhibitor". The Journal of Antimicrobial Chemotherapy. 54 (2): 333–40. doi:10.1093/jac/dkh330. PMID 15231762.
  8. ^ Eckert DM, Kim PS (September 2001). "Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region". Proceedings of the National Academy of Sciences of the United States of America. 98 (20): 11187–11192. Bibcode:2001PNAS...9811187E. doi:10.1073/pnas.201392898. PMC 58705. PMID 11572974.
  9. ^ Chen, Yu A.; Scheller, Richard H. (2001-02). "SNARE-mediated membrane fusion". Nature Reviews Molecular Cell Biology. 2 (2): 98–106. doi:10.1038/35052017. ISSN 1471-0072. {{cite journal}}: Check date values in: |date= (help)
  10. ^ Truebestein, Linda; Leonard, Thomas A. (2016-09). "Coiled‐coils: The long and short of it". BioEssays. 38 (9): 903–916. doi:10.1002/bies.201600062. ISSN 0265-9247. PMC 5082667. PMID 27492088. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  11. ^ Linstedt, Adam D.; Jesch, Stephen A.; Mehta, Amy; Lee, Tina H.; Garcia-Mata, Rafael; Nelson, David S.; Sztul, Elizabeth (2000-04). "Binding Relationships of Membrane Tethering Components". Journal of Biological Chemistry. 275 (14): 10196–10201. doi:10.1074/jbc.275.14.10196. ISSN 0021-9258. {{cite journal}}: Check date values in: |date= (help)CS1 maint: unflagged free DOI (link)
  12. ^ Witkos, Tomasz M.; Lowe, Martin (2016-01-11). "The Golgin Family of Coiled-Coil Tethering Proteins". Frontiers in Cell and Developmental Biology. 3. doi:10.3389/fcell.2015.00086. ISSN 2296-634X. PMC 4707255. PMID 26793708.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  13. ^ Jeyaprakash, A. Arockia; Santamaria, Anna; Jayachandran, Uma; Chan, Ying Wai; Benda, Christian; Nigg, Erich A.; Conti, Elena (2012-05). "Structural and Functional Organization of the Ska Complex, a Key Component of the Kinetochore-Microtubule Interface". Molecular Cell. 46 (3): 274–286. doi:10.1016/j.molcel.2012.03.005. ISSN 1097-2765. {{cite journal}}: Check date values in: |date= (help); no-break space character in |first4= at position 5 (help); no-break space character in |first6= at position 6 (help); no-break space character in |first= at position 3 (help)
  14. ^ Deiss S, Hernandez Alvarez B, Bär K, Ewers CP, Coles M, Albrecht R, Hartmann MD (June 2014). "Your personalized protein structure: Andrei N. Lupas fused to GCN4 adaptors". Journal of Structural Biology. 186 (3): 380–5. doi:10.1016/j.jsb.2014.01.013. PMID 24486584.
  15. ^ Chou, Hui-Ting; Apelt, Luise; Farrell, Daniel P.; White, Susan Roehl; Woodsmith, Jonathan; Svetlov, Vladimir; Goldstein, Jaclyn S.; Nager, Andrew R.; Li, Zixuan; Muller, Jean; Dollfus, Helene; Nudler, Evgeny; Stelzl, Ulrich; DiMaio, Frank; Nachury, Maxance V.; Walz, Thomas (3 September 2019). "The Molecular Architecture of Native BBSome Obtained by an Integrated Structural Approach". Structure. 27 (9): 1384–1394. doi:10.1016/j.str.2019.06.006. PMC 6726506. PMID 31303482.
  16. ^ Ludlam, WG; Aoba, T; Cuéllar, J; Bueno-Carrasco, MT; Makaju, A; Moody, JD; Franklin, S; Valpuesta, JM; Willardson, BM (17 September 2019). "Molecular architecture of the Bardet-Biedl syndrome protein 2-7-9 subcomplex". The Journal of Biological Chemistry. 294 (44): 16385–16399. doi:10.1074/jbc.RA119.010150. PMC 6827290. PMID 31530639.
  17. ^ Cabezon, Elena; Butler, P. Jonathan G.; Runswick, Michael J.; Walker, John E. (2000-08). "Modulation of the Oligomerization State of the Bovine F1-ATPase Inhibitor Protein, IF1, by pH". Journal of Biological Chemistry. 275 (33): 25460–25464. doi:10.1074/jbc.M003859200. {{cite journal}}: Check date values in: |date= (help)CS1 maint: unflagged free DOI (link)
  18. ^ Park, Won Min (2020-05-19). "Coiled-Coils: The Molecular Zippers that Self-Assemble Protein Nanostructures". International Journal of Molecular Sciences. 21 (10): 3584. doi:10.3390/ijms21103584. ISSN 1422-0067. PMC 7278914. PMID 32438665.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  19. ^ a b Lapenta, Fabio; Aupič, Jana; Strmšek, Žiga; Jerala, Roman (2018). "Coiled coil protein origami: from modular design principles towards biotechnological applications". Chemical Society Reviews. 47 (10): 3530–3542. doi:10.1039/C7CS00822H. ISSN 0306-0012.
  20. ^ a b c d Jorgensen, Michael D.; Chmielewski, Jean (2022). "Recent advances in coiled-coil peptide materials and their biomedical applications". Chemical Communications. 58 (83): 11625–11636. doi:10.1039/d2cc04434j. ISSN 1359-7345.
  21. ^ McFarlane, Ainsley A.; Orriss, George L.; Stetefeld, Jörg (2009-12). "The use of coiled-coil proteins in drug delivery systems". European Journal of Pharmacology. 625 (1–3): 101–107. doi:10.1016/j.ejphar.2009.05.034. PMC 7094320. PMID 19835864. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  22. ^ Schroeder, Ulrich; Graff, Alexandra; Buchmeier, Sabine; Rigler, Per; Silvan, Unai; Tropel, David; Jockusch, Brigitte M.; Aebi, Ueli; Burkhard, Peter; Schoenenberger, Cora-Ann (2009-03). "Peptide Nanoparticles Serve as a Powerful Platform for the Immunogenic Display of Poorly Antigenic Actin Determinants". Journal of Molecular Biology. 386 (5): 1368–1381. doi:10.1016/j.jmb.2008.11.023. ISSN 0022-2836. {{cite journal}}: Check date values in: |date= (help)
  23. ^ Park, Won Min (2020-01). "Coiled-Coils: The Molecular Zippers that Self-Assemble Protein Nanostructures". International Journal of Molecular Sciences. 21 (10): 3584. doi:10.3390/ijms21103584. ISSN 1422-0067. PMC 7278914. PMID 32438665. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  24. ^ Dexter, A. F.; Fletcher, N. L.; Creasey, R. G.; Filardo, F.; Boehm, M. W.; Jack, K. S. (2017). "Fabrication and characterization of hydrogels formed from designer coiled-coil fibril-forming peptides". RSC Advances. 7 (44): 27260–27271. doi:10.1039/C7RA02811C. ISSN 2046-2069. {{cite journal}}: no-break space character in |first2= at position 3 (help)
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