Editing Coiled coil (section)

===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>