Membrane fusion protein
Membrane fusion proteins (not to be confused with chimeric or fusion proteins) are proteins that cause fusion of biological membranes. Membrane fusion is critical for many biological processes, especially in eukaryotic development and viral entry. Fusion proteins can originate from genes encoded by infectious enveloped viruses, ancient retroviruses integrated into the host genome,[1] or solely by the host genome.[2] Post-transcriptional modifications made to the fusion proteins by the host, namely addition and modification of glycans and acetyl groups, can drastically affect fusogenicity (the ability to fuse).[3]
Fusion in eukaryotes
[edit]Eukaryotic genomes contain several gene families, of host and viral origin, which encode products involved in driving membrane fusion. While adult somatic cells do not typically undergo membrane fusion under normal conditions, gametes and embryonic cells follow developmental pathways to non-spontaneously drive membrane fusion, such as in placental formation, syncytiotrophoblast formation, and neurodevelopment. Fusion pathways are also involved in the development of musculoskeletal and nervous system tissues. Vesicle fusion events involved in neurotransmitter trafficking also relies on the catalytic activity of fusion proteins.
The SNARE family include bona fide eukaryotic fusion proteins. They are only found in eukaryotes and their closest archaeal relatives like Heimdallarchaeota.[4]
Retroviral
[edit]These proteins originate from the env gene of endogenous retroviruses. They are domesticated viral class I fusion proteins.
HAP2 family
[edit]HAP2 is a domesticated viral class II fusion protein found in diverse eukaryotes including Toxoplasma, vascular plants, and fruit flies. This protein is essential for gamete fusion in these organisms.[5]
Pathogenic viral fusion
[edit]Enveloped viruses readily overcome the thermodynamic barrier of merging two plasma membranes by storing kinetic energy in fusion (F) proteins. F proteins can be independently expressed on host cell surfaces which can either (1) drive the infected cell to fuse with neighboring cells, forming a syncytium, or (2) be incorporated into a budding virion from the infected cell which leads to the full emancipation of plasma membrane from the host cell. Some F components solely drive fusion while a subset of F proteins can interact with host factors. There are four groups of fusion proteins categorized by their structure and mechanism of fusion.[6]
Class I
[edit]Class I fusion proteins resemble influenzavirus hemagglutinin in their structure. Post-fusion, the active site has a trimer of α-helical coiled-coils. The binding domain is rich in α-helices and hydrophobic fusion peptides located near the N-terminus. Fusion conformation change can often be controlled by pH.[7][8]
Class II
[edit]Class II proteins are dominant in β-sheets and the catalytic sites are localized in the core region. The peptide regions required to drive fusion are formed from the turns between the β-sheets.[7][8]
Class III
[edit]Class III fusion proteins are distinct from I and II. They typically consist of 5 structural domains, where domain 1 and 2 localized to the C-terminal end often contain more β-sheets and domains 2-5 closer to the N-terminal side are richer in α-helices. In the pre-fusion state, the later domains nest and protect domain 1 (i.e. domain 1 is protected by domain 2, which is nested in domain 3, which is protected by domain 4). Domain 1 contains the catalytic site for membrane fusion.[7][8]
Class IV
[edit]Class IV fusion proteins, better known as fusion-associated small transmembrane proteins (FAST), are the smallest type of fusion protein. They are found in reoviruses, which are non-enveloped viruses and are specialized for cell-cell rather than virus-cell fusion, forming syncytia. They are the only known membrane fusion proteins found in non-enveloped viruses.[9][10]
Examples
[edit]| Fusion protein | Abbreviation | Class | Virus family | Example viruses | Reference |
|---|---|---|---|---|---|
| Coronavirus spike protein | S | I | Coronaviridae | SARS-CoV, SARS-CoV-2 | [11][12] |
| Ebolavirus glycoprotein | GP | I | Filoviridae | Zaire-, Sudan- ebolaviruses, Marburgvirus | [6][13] |
| Glycoprotein 41 | Gp41 | I | Retroviridae | HIV | [6][13] |
| Hemagglutinin | H, HA, HN | I | Orthomyxoviridae, Paramyxoviridae | Influenza virus, measles virus, mumps virus | [6][13] |
| Alphavirus envelope protein E1 | E1 | II | Togaviridae | Semliki Forest virus | [6][13] |
| Flavivirus envelope protein | E | II | Flaviviridae | Dengue virus, West Nile virus | [6][13] |
| Herpesvirus glycoprotein B | gB | III | Herpesviridae | HSV-1 | [6][14] |
| VSV G | G | III | Rhabdoviridae | Vesicular stomatitis virus, rabies lyssavirus | [6][14] |
| Fusion-associated small transmembrane protein | FAST | IV | Reoviridae | Avian orthoreovirus | [6][10] |
See also
[edit]References
[edit]- ^ Classification of viral fusion proteins in TCDB database
- ^ Klapper R, Stute C, Schomaker O, Strasser T, Janning W, Renkawitz-Pohl R, Holz A (January 2002). "The formation of syncytia within the visceral musculature of the Drosophila midgut is dependent on duf, sns and mbc". Mechanisms of Development. 110 (1–2): 85–96. doi:10.1016/S0925-4773(01)00567-6. PMID 11744371.
- ^ Ortega V, Stone JA, Contreras EM, Iorio RM, Aguilar HC (January 2019). "Addicted to sugar: roles of glycans in the order Mononegavirales". Glycobiology. 29 (1): 2–21. doi:10.1093/glycob/cwy053. PMC 6291800. PMID 29878112.
- ^ Neveu E, Khalifeh D, Salamin N, Fasshauer D (July 2020). "Prototypic SNARE Proteins Are Encoded in the Genomes of Heimdallarchaeota, Potentially Bridging the Gap between the Prokaryotes and Eukaryotes" (PDF). Current Biology. 30 (13): 2468–2480.e5. doi:10.1016/j.cub.2020.04.060. PMID 32442459. S2CID 218762979.
- ^ Fédry J, Liu Y, Péhau-Arnaudet G, Pei J, Li W, Tortorici MA, et al. (February 2017). "The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein". Cell. 168 (5): 904–915.e10. doi:10.1016/j.cell.2017.01.024. PMC 5332557. PMID 28235200.
- ^ a b c d e f g h i Podbilewicz, Benjamin (11 October 2014). "Virus and Cell Fusion Mechanisms". Annual Review of Cell and Developmental Biology. 30 (1): 111–139. doi:10.1146/annurev-cellbio-101512-122422. PMID 25000995.
- ^ a b c Backovic M, Jardetzky TS (April 2009). "Class III viral membrane fusion proteins". Current Opinion in Structural Biology. 19 (2): 189–96. doi:10.1016/j.sbi.2009.02.012. PMC 3076093. PMID 19356922.
- ^ a b c White JM, Delos SE, Brecher M, Schornberg K (2008). "Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme". Critical Reviews in Biochemistry and Molecular Biology. 43 (3): 189–219. doi:10.1080/10409230802058320. PMC 2649671. PMID 18568847.
- ^ Shmulevitz, Maya; Duncan, Roy (1 March 2000). "A new class of fusion-associated small transmembrane (FAST) proteins encoded by the non-enveloped fusogenic reoviruses". The EMBO Journal. 19 (5): 902–912. doi:10.1093/emboj/19.5.902. PMC 305630. PMID 10698932.
- ^ a b Ciechonska, Marta; Duncan, Roy (December 2014). "Reovirus FAST proteins: virus-encoded cellular fusogens". Trends in Microbiology. 22 (12): 715–724. doi:10.1016/j.tim.2014.08.005. PMID 25245455.
- ^ Li, Fang (29 September 2016). "Structure, Function, and Evolution of Coronavirus Spike Proteins". Annual Review of Virology. 3 (1): 237–261. doi:10.1146/annurev-virology-110615-042301. PMC 5457962. PMID 27578435.
- ^ Zhu, Chaogeng; He, Guiyun; Yin, Qinqin; Zeng, Lin; Ye, Xiangli; Shi, Yongzhong; Xu, Wei (October 2021). "Molecular biology of the SARs-CoV-2 spike protein: A review of current knowledge". Journal of Medical Virology. 93 (10): 5729–5741. doi:10.1002/jmv.27132. PMC 8427004. PMID 34125455.
- ^ a b c d e White, Judith M.; Whittaker, Gary R. (June 2016). "Fusion of Enveloped Viruses in Endosomes". Traffic. 17 (6): 593–614. doi:10.1111/tra.12389. PMC 4866878. PMID 26935856.
- ^ a b Baquero, Eduard; Albertini, Aurélie AV; Gaudin, Yves (August 2015). "Recent mechanistic and structural insights on class III viral fusion glycoproteins". Current Opinion in Structural Biology. 33: 52–60. doi:10.1016/j.sbi.2015.07.011. PMID 26277251.
External links
[edit]- Membrane+fusion+proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)