Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1
Binding of herpes simplex virus (HSV) glycoprotein D (gD) to a cell surface receptor is required to trigger membrane fusion during entry into host cells. Nectin-1 is a cell adhesion molecule and the main HSV receptor in neurons and epithelial cells. We report the structure of gD bound to nectin-1 determined by x-ray crystallography to 4.0 Å resolution. The structure reveals that the nectin-1 binding site on gD differs from the binding site of the HVEM receptor. A surface on the first Ig-domain of nectin-1, which mediates homophilic interactions of Ig-like cell adhesion molecules, buries an area composed by residues from both the gD N- and C-terminal extensions. Phenylalanine 129, at the tip of the loop connecting β-strands F and G of nectin-1, protrudes into a groove on gD, which is otherwise occupied by C-terminal residues in the unliganded gD and by N-terminal residues in the gD/HVEM complex. Notably, mutation of Phe129 to alanine prevents nectin-1 binding to gD and HSV entry. Together these data are consistent with previous studies showing that gD disrupts the normal nectin-1 homophilic interactions. Furthermore, the structure of the complex supports a model in which gD-receptor binding triggers HSV entry through receptor-mediated displacement of the gD C-terminal region.
Vyšlo v časopise:
Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1. PLoS Pathog 7(9): e32767. doi:10.1371/journal.ppat.1002277
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002277
Souhrn
Binding of herpes simplex virus (HSV) glycoprotein D (gD) to a cell surface receptor is required to trigger membrane fusion during entry into host cells. Nectin-1 is a cell adhesion molecule and the main HSV receptor in neurons and epithelial cells. We report the structure of gD bound to nectin-1 determined by x-ray crystallography to 4.0 Å resolution. The structure reveals that the nectin-1 binding site on gD differs from the binding site of the HVEM receptor. A surface on the first Ig-domain of nectin-1, which mediates homophilic interactions of Ig-like cell adhesion molecules, buries an area composed by residues from both the gD N- and C-terminal extensions. Phenylalanine 129, at the tip of the loop connecting β-strands F and G of nectin-1, protrudes into a groove on gD, which is otherwise occupied by C-terminal residues in the unliganded gD and by N-terminal residues in the gD/HVEM complex. Notably, mutation of Phe129 to alanine prevents nectin-1 binding to gD and HSV entry. Together these data are consistent with previous studies showing that gD disrupts the normal nectin-1 homophilic interactions. Furthermore, the structure of the complex supports a model in which gD-receptor binding triggers HSV entry through receptor-mediated displacement of the gD C-terminal region.
Zdroje
1. HeldweinEEKrummenacherC 2008 Entry of herpesviruses into mammalian cells. Cell Mol Life Sci 65 1653 1668
2. ConnollySAJacksonJOJardetzkyTSLongneckerR 2011 Fusing structure and function: a structural view of the herpesvirus entry machinery. Nat Rev Microbiol 9 369 381
3. EisenbergRJHeldweinEECohenGHKrummenacherC 2011 Recent progress in understanding herpes simplex virus entry: relationship of structure to function. WellerSK Alphaherpesviruses: Molecular and cellular Biology Norwich, UK Horizon Scientific Press 131 152
4. AtanasiuDSawWTCohenGHEisenbergRJ 2010 Cascade of events governing cell-cell fusion induced by herpes simplex virus glycoproteins gD, gH/gL, and gB. J Virol 84 12292 12299
5. ChowdaryTKCairnsTMAtanasiuDCohenGHEisenbergRJ 2010 Crystal structure of the conserved herpesvirus fusion regulator complex gH-gL. Nat Struct Mol Biol 17 882 888
6. MilneRSNicolaAVWhitbeckJCEisenbergRJCohenGH 2005 Glycoprotein D receptor-dependent, low-pH-independent endocytic entry of herpes simplex virus type 1. J Virol 79 6655 6663
7. NicolaAVHouJMajorEOStrausSE 2005 Herpes simplex virus type 1 enters human epidermal keratinocytes, but not neurons, via a pH-dependent endocytic pathway. J Virol 79 7609 7616
8. NicolaAVStrausSE 2004 Cellular and viral requirements for rapid endocytic entry of herpes simplex virus. J Virol 78 7508 7517
9. MontgomeryRIWarnerMSLumBJSpearPG 1996 Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Cell 87 427 436
10. TiwariVClementCScanlanPMKowlessurDYueBY 2005 A role for herpesvirus entry mediator as the receptor for herpes simplex virus 1 entry into primary human trabecular meshwork cells. J Virol 79 13173 13179
11. AkhtarJTiwariVOhMJKovacsMJaniA 2008 HVEM and Nectin-1 are the Major Mediators of Herpes Simplex Virus 1 (HSV-1) Entry into Human Conjunctival Epithelium. Invest Ophthalmol Vis Sci 49 4026 4035
12. KrummenacherCBaribaudFPonce De LeonMBaribaudIWhitbeckJC 2004 Comparative usage of herpesvirus entry mediator A and nectin-1 by laboratory strains and clinical isolates of herpes simplex virus. Virology 322 286 299
13. SimpsonSAManchakMDHagerEJKrummenacherCWhitbeckJC 2005 Nectin-1/HveC Mediates herpes simplex virus type 1 entry into primary human sensory neurons and fibroblasts. J Neurovirol 11 208 218
14. GalenBCheshenkoNTuyamaARamratnamBHeroldBC 2006 Access to nectin favors herpes simplex virus infection at the apical surface of polarized human epithelial cells. J Virol 80 12209 12218
15. HuberMTWisnerTWHegdeNRGoldsmithKARauchDA 2001 Herpes Simplex Virus with Highly Reduced gD Levels Can Efficiently Enter and Spread between Human Keratinocytes. J Virol 75 10309 10318
16. TiwariVClementCXuDValyi-NagyTYueBY 2006 Role for 3-o-sulfated heparan sulfate as the receptor for herpes simplex virus type 1 entry into primary human corneal fibroblasts. J Virol Methods 80 8970 8980
17. DelboyMGPattersonJLHollanderAMNicolaAV 2006 Nectin-2-mediated entry of a syncytial strain of herpes simplex virus via pH-independent fusion with the plasma membrane of Chinese hamster ovary cells. Virol J 3 105
18. StilesKMMilneRSCohenGHEisenbergRJKrummenacherC 2008 The herpes simplex virus receptor nectin-1 is down-regulated after trans-interaction with glycoprotein D. Virology 373 98 111
19. StilesKMKrummenacherC 2010 Glycoprotein D actively induces rapid internalization of two nectin-1 isoforms during herpes simplex virus entry. Virology 399 109 119
20. StilesKMWhitbeckJCLouHCohenGHEisenbergRJ 2010 Herpes simplex virus glycoprotein D interferes with binding of herpesvirus entry mediator to its ligands through downregulation and direct competition. J Virol 84 11646 11660
21. CarfiAWillisSHWhitbeckJCKrummenacherCCohenGH 2001 Herpes simplex virus glycoprotein D bound to the human receptor HveA. Mol Cell 8 169 179
22. KrummenacherCSupekarVMWhitbeckJCLazearEConnollySA 2005 Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry. EMBO J 24 4144 4153
23. ConnollySALandsburgDJCarfiAWileyDCCohenGH 2003 Structure-based mutagenesis of herpes simplex virus glycoprotein D defines three critical regions at the gD/HveA interface. J Virol 77 8127 8140
24. YoonMZagoAShuklaDSpearPG 2003 Mutations in the N termini of herpes simplex virus type 1 and 2 gDs alter functional interactions with the entry/fusion receptors HVEM, Nectin-2, and 3-O-sulfated heparan sulfate but not with Nectin-1. J Virol 77 9221 9231
25. KrummenacherCNicolaAVWhitbeckJCLouHHouW 1998 Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry. J Virol 72 7064 7074
26. NaritaHYamamotoYSuzukiMMiyazakiNYoshidaA 2011 Crystal structure of the cis-dimer of nectin-1: implications for the architecture of cell-cell junctions. J Biol Chem 286 12659 12669
27. CocchiFLopezMMenottiLAoubalaMDubreuilP 1998 The V domain of herpesvirus Ig-like receptor (HIgR) contains a major functional region in herpes simplex virus-1 entry into cells and interacts physically with the viral glycoprotein D. Proc Natl Acad Sci U S A 95 15700 15705
28. KrummenacherCRuxAHWhitbeckJCPonce de LeonMLouH 1999 The first immunoglobulin-like domain of HveC is sufficient to bind herpes simplex virus gD with full affinity while the third domain is involved in oligomerization of HveC. J Virol 73 8127 8137
29. CocchiFLopezMDubreuilPCampadelli FiumeGMenottiL 2001 Chimeric nectin1-poliovirus receptor molecules identify a nectin1 region functional in herpes simplex virus entry. J Virol 75 7987 7994
30. KrummenacherCBaribaudIPonce de LeonMWhitbeckJCLouH 2000 Localization of a binding site for herpes simplex virus glycoprotein D on the herpesvirus entry mediator C by using anti-receptor monoclonal antibodies. J Virol 74 10863 10872
31. TakaiYMiyoshiJIkedaWOgitaH 2008 Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation. Nat Rev Mol Cell Biol 9 603 615
32. KrummenacherCBaribaudISanzoJFCohenGHEisenbergRJ 2002 Effects of herpes simplex virus on structure and function of nectin- 1/HveC. J Virol 76 2424 2433
33. SakisakaTTaniguchiTNakanishiHTakahashiKMiyaharaM 2001 Requirement of interaction of nectin-1alpha/HveC with afadin for efficient cell-cell spread of herpes simplex virus type 1. J Virol 75 4734 4743
34. McCoyAJGrosse-KunstleveRWAdamsPDWinnMDStoroniLC 2007 Phaser crystallographic software. J Appl Crystallogr 40 658 674
35. SkubakPMurshudovGNPannuNS 2004 Direct incorporation of experimental phase information in model refinement. Acta Crystallogr D 60 2196 2201
36. SpearPGManojSYoonMJoggerCRZagoA 2006 Different receptors binding to distinct interfaces on herpes simplex virus gD can trigger events leading to cell fusion and viral entry. Virology 344 17 24
37. GeraghtyRJFridbergAKrummenacherCCohenGHEisenbergRJ 2001 Use of chimeric nectin-1(HveC)-related receptors to demonstrate that ability to bind alphaherpesvirus gD is not necessarily sufficient for viral entry. Virology 285 366 375
38. ZhangPMuellerSMoraisMCBatorCMBowmanVD 2008 Crystal structure of CD155 and electron microscopic studies of its complexes with polioviruses. Proc Natl Acad Sci U S A 105 18284 18289
39. KwongPDWyattRRobinsonJSweetRWSodroskiJ 1998 Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393 648 659
40. BewleyMCSpringerKZhangYBFreimuthPFlanaganJM 1999 Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR. Science 286 1579 1583
41. KirchnerEGuglielmiKMStraussHMDermodyTSStehleT 2008 Structure of reovirus sigma1 in complex with its receptor junctional adhesion molecule-A. PLoS Pathog 4 e1000235
42. MenottiLCerretaniAHengelHCampadelli-FiumeG 2008 Construction of a fully retargeted herpes simplex virus 1 recombinant capable of entering cells solely via human epidermal growth factor receptor 2. J Virol 82 10153 10161
43. MartinezWMSpearPG 2002 Amino acid substitutions in the V domain of nectin-1 (HveC) that impair entry activity for herpes simplex virus types 1 and 2 but not for Pseudorabies virus or bovine herpesvirus 1. J Virol 76 7255 7262
44. UchidaHShahWAOzuerAFramptonARJrGoinsWF 2009 Generation of herpesvirus entry mediator (HVEM)-restricted herpes simplex virus type 1 mutant viruses: resistance of HVEM-expressing cells and identification of mutations that rescue nectin-1 recognition. J Virol 83 2951 2961
45. WhitbeckJCMuggeridgeMIRuxAHouWKrummenacherC 1999 The major neutralizing antigenic site on herpes simplex virus glycoprotein D overlaps a receptor-binding domain. J Virol 73 9879 9890
46. ConnollySALandsburgDJCarfiAWhitbeckJCZuoY 2005 Potential nectin-1 binding site on herpes simplex virus glycoprotein D. J Virol 79 1282 1295
47. StruyfFMartinezWMSpearPG 2002 Mutations in the N-terminal domains of nectin-1 and nectin-2 reveal differences in requirements for entry of various alphaherpesviruses and for nectin-nectin interactions. J Virol 76 12940 12950
48. DongXXuFGongYGaoJLinP 2006 Crystal structure of the V domain of human Nectin-like molecule-1/Syncam3/Tsll1/Igsf4b, a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule. J Biol Chem 281 10610 10617
49. van RaaijMJChouinEvan der ZandtHBergelsonJMCusackS 2000 Dimeric structure of the coxsackievirus and adenovirus receptor D1 domain at 1.7 Å resolution. Structure 8 1147 1155
50. HashiguchiTOseTKubotaMMaitaNKamishikiryoJ 2011 Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM. Nat Struct Mol Biol 18 135 141
51. ConnollySALandsburgDJCarfiAWileyDCEisenbergRJ 2002 Structure-based analysis of the herpes simplex virus glycoprotein D binding site present on herpesvirus entry mediator HveA(HVEM). J Virol 76 10894 10904
52. LazearECarfiAWhitbeckJCCairnsTMKrummenacherC 2008 Engineered disulfide bonds in herpes simplex virus type 1 gD separate receptor binding from fusion initiation and viral entry. J Virol 82 700 709
53. ManojSJoggerCRMyscofskiDYoonMSpearPG 2004 Mutations in herpes simplex virus glycoprotein D that prevent cell entry via nectins and alter cell tropism. Proc Natl Acad Sci U S A 101 12414 12421
54. YoonMSpearPG 2002 Disruption of adherens junctions liberates nectin-1 to serve as receptor for herpes simplex virus and pseudorabies virus entry. J Virol 76 7203 7208
55. BergelsonJMCunninghamJADroguettGKurt-JonesEAKrithivasA 1997 Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 275 1320 1323
56. MendelsohnCLWimmerERacanielloVR 1989 Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily. Cell 56 855 865
57. BartonESForrestJCConnollyJLChappellJDLiuY 2001 Junction adhesion molecule is a receptor for reovirus. Cell 104 441 451
58. WaltersRWFreimuthPMoningerTOGanskeIZabnerJ 2002 Adenovirus fiber disrupts CAR-mediated intercellular adhesion allowing virus escape. Cell 110 789 799
59. MenottiLCocchiFCampadelli-FiumeG 2002 Critical residues in the CC′ ridge of the human nectin1 receptor V domain enable herpes simplex virus entry into the cell and act synergistically with the downstream region. Virology 301 6 12
60. GeraghtyRJKrummenacherCEisenbergRJCohenGHSpearPG 1998 Entry of alphaherpesviruses mediated by poliovirus receptor related protein 1 and poliovirus receptor. Science 280 1618 1620
61. WillisSHRuxAHPengCWhitbeckJCNicolaAV 1998 Examination of the kinetics of herpes simplex virus glycoprotein D binding to the herpesvirus entry mediator, using surface plasmon resonance. J Virol 72 5937 5947
62. GianniTAmasioMCampadelli-FiumeG 2009 Herpes simplex virus gD forms distinct complexes with fusion executors gB and gH/gL in part through the C-terminal profusion domain. J Biol Chem 284 17370 17382
63. Perez-RomeroPPerezACapulAMontgomeryRFullerAO 2005 Herpes simplex virus entry mediator associates in infected cells in a complex with viral proteins gD and at least gH. J Virol 79 4540 4544
64. CocchiFFuscoDMenottiLGianniTEisenbergRJ 2004 The soluble ectodomain of herpes simplex virus gD contains a membrane-proximal pro-fusion domain and suffices to mediate virus entry. Proc Natl Acad Sci U S A 101 7445 7450
65. ZhouGYeGJDebinskiWRoizmanB 2002 Engineered herpes simplex virus 1 is dependent on IL13Ralpha 2 receptor for cell entry and independent of glycoprotein D receptor interaction. Proc Natl Acad Sci U S A 99 15124 15129
66. ZagoAJoggerCRSpearPG 2004 Use of herpes simplex virus and pseudorabies virus chimeric glycoprotein D molecules to identify regions critical for membrane fusion. Proc Natl Acad Sci U S A 101 17498 17503
67. ZhouGAvitabileECampadelli-FiumeGRoizmanB 2003 The domains of glycoprotein D required to block apoptosis induced by herpes simplex virus 1 are largely distinct from those involved in cell-cell fusion and binding to nectin1. J Virol 77 3759 3767
68. KamiyamaHZhouGRoizmanB 2006 Herpes simplex virus 1 recombinant virions exhibiting the amino terminal fragment of urokinase-type plasminogen activator can enter cells via the cognate receptor. Gene Ther 13 621 629
69. MenottiLCerretaniACampadelli-FiumeG 2006 A herpes simplex virus recombinant that exhibits a single-chain antibody to HER2/neu enters cells through the mammary tumor receptor, independently of the gD receptors. J Virol 80 5531 5539
70. MenottiLNicolettiGGattaVCrociSLanduzziL 2009 Inhibition of human tumor growth in mice by an oncolytic herpes simplex virus designed to target solely HER-2-positive cells. Proc Natl Acad Sci U S A 106 9039 9044
71. ZhouGRoizmanB 2007 Separation of receptor-binding and profusogenic domains of glycoprotein D of herpes simplex virus 1 into distinct interacting proteins. Proc Natl Acad Sci U S A 104 4142 4146
72. OtwinowskiZMinorW 1997 Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol 276 307 326
73. CCP4 1994 The CCP4 suite: programs for protein crystallography. Acta Crystallogr D 50 760 763
74. YeatesTO 1997 Detecting and overcoming crystal twinning. Methods Enzymol 276 344 358
75. AdamsPDAfoninePVBunkocziGChenVBDavisIW 2010 PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D 66 213 221
76. KrummenacherCBaribaudIEisenbergRJCohenGH 2003 Cellular localization of nectin-1 and glycoprotein D during herpes simplex virus infection. J Virol 77 8985 8999
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