Editing Coiled coil (section)

==Biological roles==
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.<ref>{{Cite journal |last1=Rose |first1=Annkatrin |last2=Schraegle |first2=Shannon J. |last3=Stahlberg |first3=Eric A. |last4=Meier |first4=Iris |date=2005-11-16 |title=Coiled-coil protein composition of 22 proteomes – differences and common themes in subcellular infrastructure and traffic control |journal=BMC Evolutionary Biology |volume=5 |issue=1 |pages=66 |doi=10.1186/1471-2148-5-66 |issn=1471-2148 |pmc=1322226 |pmid=16288662 |bibcode=2005BMCEE...5...66R |doi-access=free }}</ref>

===Membrane fusion===
[[Image:gp41 coiled coil hexamer 1aik sideview.png|thumb|200px|right|Side view of the gp41 hexamer that initiates the entry of HIV into its target cell.]]

A coiled coil domain plays a role in [[human immunodeficiency virus type 1]] (HIV-1) infection. Viral entry into CD4-positive cells commences when three subunits of a glycoprotein 120 ([[gp120]]) bind to CD4 receptor and a coreceptor.<ref>{{cite journal |vauthors=Shaik MM, Peng H, Lu J, Rits-Volloch S, Xu C, Liao M, Chen B |date=January 2019 |title=Structural basis of coreceptor recognition by HIV-1 envelope spike |journal=Nature |volume=565 |issue=7739 |pages=318–323 |doi=10.1038/s41586-018-0804-9 |pmc=6391877 |pmid=30542158}}</ref>  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.<ref>{{cite journal |vauthors=Wilen CB, Tilton JC, Doms RW |date=August 2012 |title=HIV: cell binding and entry |journal=Cold Spring Harbor Perspectives in Medicine |volume=2 |issue=8 |pages=a006866 |doi=10.1101/cshperspect.a006866 |pmc=3405824 |pmid=22908191}}</ref> The virus then enters the cell and begins its replication.  Recently, inhibitors derived from HR2 such as [[Enfuvirtide|Fuzeon]] (DP178, T-20) that bind to the HR1 region on gp41 have been developed.<ref name="pmid152317622">{{cite journal |vauthors=Greenberg ML, Cammack N |date=August 2004 |title=Resistance to enfuvirtide, the first HIV fusion inhibitor |journal=The Journal of Antimicrobial Chemotherapy |volume=54 |issue=2 |pages=333–40 |doi=10.1093/jac/dkh330 |pmid=15231762|doi-access=free }}</ref> 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 zipper|leucine zippers]] have been developed and have shown to be more active than [[Enfuvirtide|Fuzeon]].<ref>{{cite journal |vauthors=Eckert DM, Kim PS |date=September 2001 |title=Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=98 |issue=20 |pages=11187–11192 |bibcode=2001PNAS...9811187E |doi=10.1073/pnas.201392898 |pmc=58705 |pmid=11572974 |doi-access=free}}</ref>  [[Human immunodeficiency virus type 2]] has a membrane envelope glycoprotein with similar structure to HIV-1 gp41, but containing substitutions for a glycine amino acid residue in the coiled coil domain that may impact trimer stability.<ref>{{cite journal|vauthors=Chen B, Chou JJ|title=Structure of the transmembrane domain of HIV-1 envelope glycoprotein|journal=The FEBS Journal|volume=284|pages=1171-1177|doi=10.1111/febs.13954|pmid=27868386|pmc=5448286|year=2017|doi-access=free}}</ref>

The proteins [[SNAP25|SNAP-25]], [[synaptobrevin]], and [[STX1A|syntaxin-1]] have alpha-helices which interact with each other to form a coiled-coil [[SNARE protein|SNARE complex]]. Zippering the domains together provides the necessary energy for vesicle fusion to occur.<ref>{{Cite journal |last1=Chen |first1=Yu A. |last2=Scheller |first2=Richard H. |date=February 2001 |title=SNARE-mediated membrane fusion |url=https://www.nature.com/articles/35052017 |journal=Nature Reviews Molecular Cell Biology |language=en |volume=2 |issue=2 |pages=98–106 |doi=10.1038/35052017 |pmid=11252968 |s2cid=205012830 |issn=1471-0072|url-access=subscription }}</ref>

=== Molecular spacers ===
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 ''[[Thermotoga maritima|T. maritima]]''.<ref>{{Cite journal |last1=Truebestein |first1=Linda |last2=Leonard |first2=Thomas A. |date=September 2016 |title=Coiled-coils: The long and short of it |journal=BioEssays |language=en |volume=38 |issue=9 |pages=903–916 |doi=10.1002/bies.201600062 |issn=0265-9247 |pmc=5082667 |pmid=27492088}}</ref> 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 apparatus|Golgi]] and a nearby vesicle.<ref>{{Cite journal |last1=Linstedt |first1=Adam D. |last2=Jesch |first2=Stephen A. |last3=Mehta |first3=Amy |last4=Lee |first4=Tina H. |last5=Garcia-Mata |first5=Rafael |last6=Nelson |first6=David S. |last7=Sztul |first7=Elizabeth |date=April 2000 |title=Binding Relationships of Membrane Tethering Components |journal=Journal of Biological Chemistry |volume=275 |issue=14 |pages=10196–10201 |doi=10.1074/jbc.275.14.10196 |pmid=10744704 |issn=0021-9258 |doi-access=free }}</ref> The family of proteins related to this activity of tethering vesicles to the Golgi are known as golgins.<ref>{{Cite journal |last1=Witkos |first1=Tomasz M. |last2=Lowe |first2=Martin |date=2016-01-11 |title=The Golgin Family of Coiled-Coil Tethering Proteins |journal=Frontiers in Cell and Developmental Biology |volume=3 |page=86 |doi=10.3389/fcell.2015.00086 |issn=2296-634X |pmc=4707255 |pmid=26793708 |doi-access=free }}</ref> Finally, there are several proteins with coiled-coil domains involved in the [[kinetochore]], which keeps [[Chromosome|chromosomes]] separated during [[cell division]]. These proteins include [[NDC80|Ndc-80]], and [[NUF2|Nuf2p]]. Related proteins interact with [[Microtubule|microtubules]] during cell division, of which mutation leads to cell death.<ref>{{Cite journal |last1=Jeyaprakash |first1=A. Arockia |last2=Santamaria |first2=Anna |last3=Jayachandran |first3=Uma |last4=Chan |first4=Ying Wai |last5=Benda |first5=Christian |last6=Nigg |first6=Erich A. |last7=Conti |first7=Elena |date=May 2012 |title=Structural and Functional Organization of the Ska Complex, a Key Component of the Kinetochore-Microtubule Interface |journal=Molecular Cell |volume=46 |issue=3 |pages=274–286 |doi=10.1016/j.molcel.2012.03.005 |pmid=22483620 |issn=1097-2765|doi-access=free }}</ref>

===As oligomerization tags===
Because of their specific interaction coiled coils can be used as "tags" to stabilize or enforce a specific oligomerization state.<ref name="Deiss_20142">{{cite journal |vauthors=Deiss S, Hernandez Alvarez B, Bär K, Ewers CP, Coles M, Albrecht R, Hartmann MD |date=June 2014 |title=Your personalized protein structure: Andrei N. Lupas fused to GCN4 adaptors |journal=Journal of Structural Biology |volume=186 |issue=3 |pages=380–5 |doi=10.1016/j.jsb.2014.01.013 |pmid=24486584 |doi-access=free}}</ref> A coiled coil interaction has been observed to drive the oligomerization of the [[BBS2]] and [[BBS7]] subunits of the [[BBSome]]. <ref>{{cite journal |last1=Chou |first1=Hui-Ting |last2=Apelt |first2=Luise |last3=Farrell |first3=Daniel P. |last4=White |first4=Susan Roehl |last5=Woodsmith |first5=Jonathan |last6=Svetlov |first6=Vladimir |last7=Goldstein |first7=Jaclyn S. |last8=Nager |first8=Andrew R. |last9=Li |first9=Zixuan |last10=Muller |first10=Jean |last11=Dollfus |first11=Helene |last12=Nudler |first12=Evgeny |last13=Stelzl |first13=Ulrich |last14=DiMaio |first14=Frank |last15=Nachury |first15=Maxance V. |date=3 September 2019 |title=The Molecular Architecture of Native BBSome Obtained by an Integrated Structural Approach |journal=Structure |volume=27 |issue=9 |pages=1384–1394 |doi=10.1016/j.str.2019.06.006 |pmc=6726506 |pmid=31303482 |last16=Walz |first16=Thomas}}</ref><ref>{{cite journal |last1=Ludlam |first1=WG |last2=Aoba |first2=T |last3=Cuéllar |first3=J |last4=Bueno-Carrasco |first4=MT |last5=Makaju |first5=A |last6=Moody |first6=JD |last7=Franklin |first7=S |last8=Valpuesta |first8=JM |last9=Willardson |first9=BM |date=17 September 2019 |title=Molecular architecture of the Bardet-Biedl syndrome protein 2-7-9 subcomplex. |journal=The Journal of Biological Chemistry |volume=294 |issue=44 |pages=16385–16399 |doi=10.1074/jbc.RA119.010150 |pmc=6827290 |pmid=31530639 |doi-access=free}}</ref> 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.<ref>{{Cite journal |last1=Cabezon |first1=Elena |last2=Butler |first2=P. Jonathan G. |last3=Runswick |first3=Michael J. |last4=Walker |first4=John E. |date=August 2000 |title=Modulation of the Oligomerization State of the Bovine F1-ATPase Inhibitor Protein, IF1, by pH |journal=Journal of Biological Chemistry |language=en |volume=275 |issue=33 |pages=25460–25464 |doi=10.1074/jbc.M003859200 |pmid=10831597 |doi-access=free }}</ref>  Because of their ability in driving [[Protein oligomer|protein oligomerization]], they have also been studied in their use in forming synthetic nanostructures.<ref>{{Cite journal |last=Park |first=Won Min |date=2020-05-19 |title=Coiled-Coils: The Molecular Zippers that Self-Assemble Protein Nanostructures |journal=International Journal of Molecular Sciences |language=en |volume=21 |issue=10 |pages=3584 |doi=10.3390/ijms21103584 |issn=1422-0067 |pmc=7278914 |pmid=32438665 |doi-access=free }}</ref>