{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:08:41Z","timestamp":1790435321047,"version":"4.1.0"},"reference-count":68,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["FONDECYT 1221811"],"award-info":[{"award-number":["FONDECYT 1221811"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["FONDECYT 1261422"],"award-info":[{"award-number":["FONDECYT 1261422"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["FONDECYT 3200556"],"award-info":[{"award-number":["FONDECYT 3200556"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["FONDEF TA24I10051"],"award-info":[{"award-number":["FONDEF TA24I10051"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["Basal FB210008"],"award-info":[{"award-number":["Basal FB210008"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"award":["FONDECYT 1221811"],"award-info":[{"award-number":["FONDECYT 1221811"]}],"id":[{"id":"https:\/\/ror.org\/02ap3w078","id-type":"ROR","asserted-by":"publisher"}]},{"award":["FONDECYT 1261422"],"award-info":[{"award-number":["FONDECYT 1261422"]}],"id":[{"id":"https:\/\/ror.org\/02ap3w078","id-type":"ROR","asserted-by":"publisher"}]},{"award":["FONDECYT 3200556"],"award-info":[{"award-number":["FONDECYT 3200556"]}],"id":[{"id":"https:\/\/ror.org\/02ap3w078","id-type":"ROR","asserted-by":"publisher"}]},{"award":["FONDEF TA24I10051"],"award-info":[{"award-number":["FONDEF TA24I10051"]}],"id":[{"id":"https:\/\/ror.org\/02ap3w078","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Basal FB210008"],"award-info":[{"award-number":["Basal FB210008"]}],"id":[{"id":"https:\/\/ror.org\/02ap3w078","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Andes virus (ANDV), a highly pathogenic orthohantavirus, enters host cells through low pH\u2013triggered membrane fusion mediated by the Gc glycoprotein, a class II fusion protein containing a single C-terminal transmembrane domain (TMD). While the ectodomain has been extensively characterized, the role of the TMD in late-stage fusion remains unclear. Here, we investigated the minimal functional length and sequence requirements of the ANDV Gc TMD using site-directed mutagenesis. C-terminal deletion mutants and serine-to-alanine substitutions were evaluated for protein expression, virus-like particle production, cell\u2013cell fusion, pseudotyped vector entry, and hemifusion activity. Deletion of the Gc cytoplasmic tail (CT) or a single C-terminal TMD residue was tolerated, whereas deletion of two or more residues impaired particle production and fusion, indicating that at least 21 of the 22 TMD residues are required for efficient membrane fusion and viral entry. Hemifusion assays showed that deletion of two or three residues, or substitution of the strictly conserved S1121, allowed lipid mixing but blocked progression to full fusion, while deletion of four residues also abolished hemifusion. In contrast, mutation of the less conserved S1126 had minimal effect. These results identify a precise TMD length and a conserved polar TMD residue as critical determinants of fusion pore formation in ANDV.<\/jats:p>","DOI":"10.3390\/v18060633","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:17:31Z","timestamp":1780467451000},"page":"633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Specific Determinants of the Transmembrane Region of the Andes Virus Gc Glycoprotein Drive the Transition from Membrane Hemifusion to Pore Formation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3935-4554","authenticated-orcid":false,"given":"Chantal L.","family":"M\u00e1rquez","sequence":"first","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida, Santiago 8581151, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9728-1301","authenticated-orcid":false,"given":"Fernando","family":"Villal\u00f3n-Letelier","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida, Santiago 8581151, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianina","family":"Arata-Salas","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida, Santiago 8581151, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-4780","authenticated-orcid":false,"given":"Nicole D.","family":"Tischler","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida, Santiago 8581151, Chile"},{"name":"Escuela de Bioqu\u00edmica, Facultad de Ciencias, Universidad San Sebasti\u00e1n, Santiago 7510579, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"001975","DOI":"10.1099\/jgv.0.001975","article-title":"ICTV Virus Taxonomy Profile: Hantaviridae 2024: This article is part of the ICTV Virus Taxonomy Profiles collection","volume":"105","author":"Bradfute","year":"2024","journal-title":"J. General. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1128\/CMR.00062-09","article-title":"A Global Perspective on Hantavirus Ecology, Epidemiology, and Disease","volume":"23","author":"Jonsson","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"167230","DOI":"10.1016\/j.jmb.2021.167230","article-title":"Innate Immunity to Orthohantaviruses: Could Divergent Immune Interactions Explain Host-specific Disease Outcomes?","volume":"434","author":"Kell","year":"2022","journal-title":"J. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jcv.2014.08.033","article-title":"Hantaviruses\u2014Globally emerging pathogens","volume":"64","author":"Kruger","year":"2015","journal-title":"J. Clin. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mull, N., Jackson, R., Sironen, T., and Forbes, K.M. (2020). Ecology of Neglected Rodent-Borne American Orthohantaviruses. Pathogens, 9.","DOI":"10.3390\/pathogens9050325"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.3390\/v6031317","article-title":"Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions","volume":"6","author":"Schountz","year":"2014","journal-title":"Viruses"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1056\/NEJMoa2009040","article-title":"\u201cSuper-Spreaders\u201d and Person-to-Person Transmission of Andes Virus in Argentina","volume":"383","author":"Alonso","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/S1473-3099(24)00142-7","article-title":"Viral shedding and viraemia of Andes virus during acute hantavirus infection: A prospective study","volume":"24","author":"Henriquez","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e371","DOI":"10.1016\/S1473-3099(23)00128-7","article-title":"Hantavirus in humans: A review of clinical aspects and management","volume":"23","author":"Vial","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/bs.aivir.2019.07.002","article-title":"Hantavirus entry: Perspectives and recent advances","volume":"104","author":"Mittler","year":"2019","journal-title":"Adv. Virus Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.coviro.2021.07.009","article-title":"The surface glycoproteins of hantaviruses","volume":"50","author":"Rey","year":"2021","journal-title":"Curr. Opin. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1099\/jgv.0.000269","article-title":"Acidification triggers Andes hantavirus membrane fusion and rearrangement of Gc into a stable post-fusion homotrimer","volume":"96","author":"Bignon","year":"2015","journal-title":"J. General. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00801-15","DOI":"10.1128\/mBio.00801-15","article-title":"Haploid Genetic Screen Reveals a Profound and Direct Dependence on Cholesterol for Hantavirus Membrane Fusion","volume":"6","author":"Kleinfelter","year":"2015","journal-title":"mBio"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Guardado-Calvo, P., Bignon, E.A., Stettner, E., Jeffers, S.A., P\u00e9rez-Vargas, J., Pehau-Arnaudet, G., Tortorici, M.A., Jestin, J.-L., England, P., and Tischler, N.D. (2016). Mechanistic Insight into Bunyavirus-Induced Membrane Fusion from Structure-Function Analyses of the Hantavirus Envelope Glycoprotein Gc. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005813"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.cell.2020.08.023","article-title":"The Hantavirus Surface Glycoprotein Lattice and Its Fusion Control Mechanism","volume":"183","author":"Serris","year":"2020","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.virol.2015.03.043","article-title":"Viral membrane fusion","volume":"479\u2013480","author":"Harrison","year":"2015","journal-title":"Virology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Barrett, C.T., and Dutch, R.E. (2020). Viral Membrane Fusion and the Transmembrane Domain. Viruses, 12.","DOI":"10.3390\/v12070693"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1007\/s00018-007-6439-x","article-title":"The role of transmembrane domains in membrane fusion","volume":"64","author":"Langosch","year":"2007","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/10409230802058320","article-title":"Structures and mechanisms of viral membrane fusion proteins: Multiple variations on a common theme","volume":"43","author":"White","year":"2008","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1099\/vir.0.2008\/001792-0","article-title":"Formation of bovine viral diarrhea virus E1\u2013E2 heterodimers is essential for virus entry and depends on charged residues in the transmembrane domains","volume":"89","author":"Ronecker","year":"2008","journal-title":"J. General. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1128\/JVI.77.6.3441-3450.2003","article-title":"Interactions between the Transmembrane Segments of the Alphavirus E1 and E2 Proteins Play a Role in Virus Budding and Fusion","volume":"77","author":"Garoff","year":"2003","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.virol.2004.11.035","article-title":"The conserved glycine residues in the transmembrane domain of the Semliki Forest virus fusion protein are not required for assembly and fusion","volume":"332","author":"Liao","year":"2005","journal-title":"Virology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nsmb.2463","article-title":"Cryo-EM structure of the mature dengue virus at 3.5-\u00c5 resolution","volume":"20","author":"Zhang","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1126\/science.aaf5316","article-title":"The 3.8 \u00c5 resolution cryo-EM structure of Zika virus","volume":"352","author":"Sirohi","year":"2016","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3854","DOI":"10.1038\/emboj.2011.261","article-title":"4.4 \u00c5 cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus: 4.4 \u00c5 cryo-EM structure of an enveloped alphavirus","volume":"30","author":"Zhang","year":"2011","journal-title":"EMBO J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.virol.2014.02.015","article-title":"Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses","volume":"454\u2013455","author":"Wang","year":"2014","journal-title":"Virology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/bs.aivir.2017.02.002","article-title":"The Envelope Proteins of the Bunyavirales","volume":"Volume 98","author":"Rey","year":"2017","journal-title":"Advances in Virus Research"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.virusres.2010.07.001","article-title":"Development of a lentiviral vector system to study the role of the Andes virus glycoproteins","volume":"153","author":"Darlix","year":"2010","journal-title":"Virus Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5046","DOI":"10.1128\/JVI.02409-08","article-title":"Andes Virus Antigens Are Shed in Urine of Patients with Acute Hantavirus Cardiopulmonary Syndrome","volume":"83","author":"Godoy","year":"2009","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1006\/jmbi.2000.4315","article-title":"Predicting transmembrane protein topology with a hidden markov model: Application to complete genomes11Edited by F. Cohen","volume":"305","author":"Krogh","year":"2001","journal-title":"J. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1128\/JVI.03118-13","article-title":"Hantavirus Gn and Gc Glycoproteins Self-Assemble into Virus-Like Particles","volume":"88","author":"Bulling","year":"2014","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/0042-6822(73)90341-3","article-title":"A new technique for the assay of infectivity of human adenovirus 5 DNA","volume":"52","author":"Graham","year":"1973","journal-title":"Virology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1099\/vir.0.027235-0","article-title":"Aromatic and polar residues spanning the candidate fusion peptide of the Andes virus Gc protein are essential for membrane fusion and infection","volume":"92","author":"Barriga","year":"2011","journal-title":"J. General. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1083\/jcb.200501093","article-title":"SNAREs can promote complete fusion and hemifusion as alternative outcomes","volume":"170","author":"Giraudo","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8307","DOI":"10.1128\/JVI.74.18.8307-8315.2000","article-title":"Development of Minimal Lentivirus Vectors Derived from Simian Immunodeficiency Virus (SIVmac251) and Their Use for Gene Transfer into Human Dendritic Cells","volume":"74","author":"Mangeot","year":"2000","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1006\/mthe.2002.0541","article-title":"High Levels of Transduction of Human Dendritic Cells with Optimized SIV Vectors","volume":"5","author":"Mangeot","year":"2002","journal-title":"Mol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1016\/j.cell.2026.01.030","article-title":"High-resolution in situ structures of hantavirus glycoprotein tetramers","volume":"189","author":"Guo","year":"2026","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1021\/mp900241t","article-title":"The Mechanism of Polyplex Internalization into Cells: Testing the GM1\/Caveolin-1 Lipid Raft Mediated Endocytosis Pathway","volume":"7","author":"Qi","year":"2010","journal-title":"Mol. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0167-4781(97)00117-6","article-title":"Chinese hamster ovary cells lacking GM1 and GD1a synthesize gangliosides upon transfection with human GM2 synthase","volume":"1354","author":"Daniotti","year":"1997","journal-title":"Biochim. Biophys. Acta (BBA) Gene Struct. Expr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/j.1365-2958.1994.tb00467.x","article-title":"Galactose-binding site in Escherichia coli heat-labile enterotoxin (LT) and cholera toxin (CT)","volume":"13","author":"Merritt","year":"1994","journal-title":"Mol. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3857","DOI":"10.1002\/j.1460-2075.1990.tb07604.x","article-title":"Fatty acids on the A\/Japan\/305\/57 influenza virus hemagglutinin have a role in membrane fusion","volume":"9","author":"Naeve","year":"1990","journal-title":"EMBO J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4603","DOI":"10.1128\/JVI.76.9.4603-4611.2002","article-title":"Fatty acids on the A\/USSR\/77 influenza virus hemagglutinin facilitate the transition from hemifusion to fusion pore formation","volume":"76","author":"Sakai","year":"2002","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6616","DOI":"10.1128\/jvi.66.11.6616-6625.1992","article-title":"Truncation of the human immunodeficiency virus type 1 transmembrane glycoprotein cytoplasmic domain blocks virus infectivity","volume":"66","author":"Dubay","year":"1992","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1128\/jvi.68.1.570-574.1994","article-title":"Mutations in the membrane-spanning domain of the human immunodeficiency virus envelope glycoprotein that affect fusion activity","volume":"68","author":"Owens","year":"1994","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"11588","DOI":"10.1128\/JVI.00914-09","article-title":"Truncation of the membrane-spanning domain of human immunodeficiency virus type 1 envelope glycoprotein defines elements required for fusion, incorporation, and infectivity","volume":"83","author":"Yue","year":"2009","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9601","DOI":"10.1128\/JVI.75.20.9601-9612.2001","article-title":"Mutations within the putative membrane-spanning domain of the simian immunodeficiency virus transmembrane glycoprotein define the minimal requirements for fusion, incorporation, and infectivity","volume":"75","author":"West","year":"2001","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7067","DOI":"10.1128\/JVI.77.12.7067-7077.2003","article-title":"Progressive truncations C terminal to the membrane-spanning domain of simian immunodeficiency virus Env reduce fusogenicity and increase concentration dependence of Env for fusion","volume":"77","author":"Lin","year":"2003","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1083\/jcb.151.2.425","article-title":"The transmembrane domain of influenza hemagglutinin exhibits a stringent length requirement to support the hemifusion to fusion transition","volume":"151","author":"Armstrong","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1083\/jcb.131.3.679","article-title":"GPI-anchored influenza hemagglutinin induces hemifusion to both red blood cell and planar bilayer membranes","volume":"131","author":"Melikyan","year":"1995","journal-title":"J. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1083\/jcb.136.5.995","article-title":"Inner but Not Outer Membrane Leaflets Control the Transition from Glycosylphosphatidylinositol-anchored Influenza Hemagglutinin-induced Hemifusion to Full Fusion","volume":"136","author":"Melikyan","year":"1997","journal-title":"J. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0092-8674(94)90344-1","article-title":"Lipid-anchored influenza hemagglutinin promotes hemifusion, not complete fusion","volume":"76","author":"Kemble","year":"1994","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.cell.2005.10.015","article-title":"Membrane Hemifusion: Crossing a Chasm in Two Leaps","volume":"123","author":"Chernomordik","year":"2005","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.1073\/pnas.0307332101","article-title":"Modulation of the bilayer thickness of exocytic pathway membranes by membrane proteins rather than cholesterol","volume":"101","author":"Mitra","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.1073\/pnas.95.7.3425","article-title":"The transmembrane domain in viral fusion: Essential role for a conserved glycine residue in vesicular stomatitis virus G protein","volume":"95","author":"Cleverley","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1091\/mbc.10.6.1821","article-title":"Amino Acid Sequence Requirements of the Transmembrane and Cytoplasmic Domains of Influenza Virus Hemagglutinin for Viable Membrane Fusion","volume":"10","author":"Melikyan","year":"1999","journal-title":"Mol. Biol. Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4377","DOI":"10.1128\/JVI.02458-10","article-title":"The Unique Transmembrane Hairpin of Flavivirus Fusion Protein E Is Essential for Membrane Fusion","volume":"85","author":"Fritz","year":"2011","journal-title":"J. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6365","DOI":"10.1128\/JVI.00447-16","article-title":"Membrane Anchors of the Structural Flavivirus Proteins and Their Role in Virus Assembly","volume":"90","author":"Blazevic","year":"2016","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1091\/mbc.10.9.2803","article-title":"The Role of the Membrane-spanning Domain Sequence in Glycoprotein-mediated Membrane Fusion","volume":"10","author":"Taylor","year":"1999","journal-title":"Mol. Biol. Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1021\/bi201721r","article-title":"HIV-1 gp41 Transmembrane Domain Interacts with the Fusion Peptide: Implication in Lipid Mixing and Inhibition of Virus\u2013Cell Fusion","volume":"51","author":"Reuven","year":"2012","journal-title":"Biochemistry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3958","DOI":"10.1073\/pnas.1019668108","article-title":"Transmembrane orientation and possible role of the fusogenic peptide from parainfluenza virus 5 (PIV5) in promoting fusion","volume":"108","author":"Donald","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"E7987","DOI":"10.1073\/pnas.1708052114","article-title":"Structure of the Ebola virus envelope protein MPER\/TM domain and its interaction with the fusion loop explains their fusion activity","volume":"114","author":"Lee","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"8246","DOI":"10.1021\/jacs.8b04010","article-title":"Oligomeric Structure and Three-Dimensional Fold of the HIV gp41 Membrane-Proximal External Region and Transmembrane Domain in Phospholipid Bilayers","volume":"140","author":"Kwon","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1021\/acs.chemrev.5c00581","article-title":"Conformational Flexibility of Transmembrane Helices: How it Works and Where it Matters","volume":"126","author":"Langosch","year":"2026","journal-title":"Chem. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1002\/pro.154","article-title":"Interaction and conformational dynamics of membrane-spanning protein helices","volume":"18","author":"Langosch","year":"2009","journal-title":"Protein Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1002\/pro.5560070423","article-title":"The dimerization motif of the glycophorin A transmembrane segment in membranes: Importance of glycine residues","volume":"7","author":"Brosig","year":"1998","journal-title":"Protein Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e1027032","DOI":"10.1080\/21690707.2015.1027032","article-title":"The intrinsic disorder alphabet. III. Dual personality of serine","volume":"3","author":"Uversky","year":"2015","journal-title":"Intrinsically Disord. Proteins"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1016\/S0006-3495(00)76514-3","article-title":"Serine and Threonine Residues Bend \u03b1-Helices in the \u03c71=g\u2212 Conformation","volume":"79","author":"Ballesteros","year":"2000","journal-title":"Biophys. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e46028","DOI":"10.7554\/eLife.46028","article-title":"Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface","volume":"8","author":"Bignon","year":"2019","journal-title":"eLife"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/6\/633\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:25:54Z","timestamp":1780467954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/6\/633"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,31]]},"references-count":68,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["v18060633"],"URL":"https:\/\/doi.org\/10.3390\/v18060633","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,31]]}}}