title: Force-induced globule-coil transition in laminin binding protein and its role for viral-cell membrane fusion.
abstract: The specific interactions of the pairs laminin binding protein (LBP)-purified tick-borne encephalitis viral surface protein E and certain recombinant fragments of this protein, as well as West Nile viral surface protein E and certain recombinant fragments of that protein, are studied by combined methods of single-molecule dynamic force spectroscopy (SMDFS), enzyme immunoassay and optical surface waves-based biosensor measurements. The experiments were performed at neutral pH (7.4) and acid pH (5.3) conditions. The data obtained confirm the role of LBP as a cell receptor for two typical viral species of the Flavivirus genus. A comparison of these data with similar data obtained for another cell receptor of this family, namely human αVβ3 integrin, reveals that both these receptors are very important. Studying the specific interaction between the cell receptors in question and specially prepared monoclonal antibodies against them, we could show that both interaction sites involved in the process of virus-cell interaction remain intact at pH 5.3. At the same time, for these acid conditions characteristic for an endosome during flavivirus-cell membrane fusion, SMDFS data reveal the existence of a force-induced (effective already for forces as small as 30-70 pN) sharp globule-coil transition for LBP and LBP-fragments of protein E complexes. We argue that this conformational transformation, being an analog of abrupt first-order phase transition and having similarity with the famous Rayleigh hydrodynamic instability, might be indispensable for the flavivirus-cell membrane fusion process.
authors.affiliation: Department of Molecular Virology for Flaviviruses and Viral Hepatitis, State Research Center for Virology and Biotechnology "Vector", Koltsovo, Novosibirsk region, 630559, Russia.
authors.forename: Boris N
authors.initials: BN
authors.lastname: Zaitsev
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Benedetti
authors.forename: Andrey G
authors.initials: AG
authors.lastname: Mikhaylov
authors.forename: Denis V
authors.initials: DV
authors.lastname: Korneev
authors.forename: Sergey K
authors.initials: SK
authors.lastname: Sekatskii
authors.forename: Tanya
authors.initials: T
authors.lastname: Karakouz
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Belavin
authors.forename: Nina A
authors.initials: NA
authors.lastname: Netesova
authors.forename: Elena V
authors.initials: EV
authors.lastname: Protopopova
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Konovalova
authors.forename: Giovanni
authors.initials: G
authors.lastname: Dietler
authors.forename: Valery B
authors.initials: VB
authors.lastname: Loktev
mesh_terms: D004669:Encephalitis Viruses, Tick-Borne / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007700:Kinetics; D007797:Laminin / Q000378:metabolism*; D008024:Ligands; D008561:Membrane Fusion; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013057:Spectrum Analysis; D013314:Stress, Mechanical; D013816:Thermodynamics; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D039302:Integrin alphaVbeta3; D007797:Laminin; D008024:Ligands; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C065696:glycoprotein E, Flavivirus
keywords: flavivirus surface protein E; flavivirus-cell membrane fusion; force-induced globule-coil transition; laminin binding protein; single-molecule dynamic force spectroscopy