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Cited by 230interferon and immune responsesCytokine Signaling Pathways and InteractionsReceptor Mechanisms and Signaling

Structural and dynamic determinants of type I interferon receptor assembly and their functional interpretation

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Piehler, Jacob, Thomas, Christoph, Garcia, K.Christopher, Schreiber, Gideon·2012·Immunological Reviews
DOI 10.1111/imr.12001PMC PMC3986811
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Abstract

Summary: Type I interferons (IFNs) form a network of homologous cytokines that bind to a shared, heterodimeric cell surface receptor and engage signaling pathways that activate innate and adaptive immune responses. The ability of IFNs to mediate differential responses through the same cell surface receptor has been subject of a controversial debate and has important medical implications. During the past decade, a comprehensive insight into the structure, energetics, and dynamics of IFN recognition by its two‐receptor subunits, as well as detailed correlations with their functional properties on the level of signal activation, gene expression, and biological responses were obtained. All type I IFNs bind the two‐receptor subunits at the same sites and form structurally very similar ternary complexes. Differential IFN activities were found to be determined by different lifetimes and ligand affinities toward the receptor subunits, which dictate assembly and dynamics of the signaling complex in the plasma membrane. We present a simple model, which explains differential IFN activities based on rapid endocytosis of signaling complexes and negative feedback mechanisms interfering with ternary complex assembly. More insight into signaling pathways as well as endosomal signaling and trafficking will be required for a comprehensive understanding, which will eventually lead to therapeutic applications of IFNs with increased efficacy.

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  • IFN-α and IFN-β have similar functionality, but IFN-β shows the highest receptor affinity, resulting in stronger IFN-driven effects.

    “While IFN-α and IFN-β have similar functionality, IFN-β shows the highest receptor affinity, resulting in stronger IFN-driven effects [27].”

    From Ectopic PU.1 Expression Provides Chimeric Antigen Receptor (CAR) T Cells with Innate Cell Capacities Including IFN-β Release (2024) · cites this paper as [27]

    The Energetics and dynamics section identifies IFNβ as the tightest-binding IFN. The Systematic correlation section says its higher affinity explains greater antiproliferative activity than IFNα2, but also says their antiviral activity is very similar. The claim overgeneralizes this into stronger IFN-driven effects overall; page numbers were not supplied for these passages. (LLM, conf=0.88)

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  1. [1]Stetson DB Medzhitov R Type I interferons in host defense Immunity 2006 25 373 381 16979569
  2. [2]Schoggins JW A diverse range of gene products are effectors of the type I interferon antiviral response Nature 2011 472 481 485 21478870 PMC3409588
  3. [3]Isaacs A Lindenmann J Virus interference. I. The interferon Proc R Soc Lond B Biol Sci 1957 147 258 267 26297790
  4. [4]Uze G Lutfalla G Gresser I Genetic transfer of a functional human interferon alpha receptor into mouse cells: cloning and expression of its cDNA Cell 1990 60 225 234 2153461
  5. [5]Novick D Cohen B Rubinstein M The human interferon alpha/beta receptor: characterization and molecular cloning Cell 1994 77 391 400 8181059
  6. [6]Cohen B Novick D Barak S Rubinstein M Ligand-induced association of the type I interferon receptor components Mol Cell Biol 1995 15 4208 4214 7623815 PMC230659
  7. [7]Decker T Muller M Stockinger S The yin and yang of type I interferon activity in bacterial infection Nat Rev Immunol 2005 5 675 687 16110316
  8. [8]Morrell CN Beta interferon suppresses the development of experimental cerebral malaria Infect Immun 2011 79 1750 1758 21245265 PMC3067534
  9. [9]Meissner NN Swain S Tighe M Harmsen A Harmsen A Role of type I IFNs in pulmonary complications of Pneumocystis murina infection J Immunol 2005 174 5462 5471 15843544
  10. [10]Moll HP Maier T Zommer A Lavoie T Brostjan C The differential activity of interferon-alpha subtypes is consistent among distinct target genes and cell types Cytokine 2011 53 52 59 20943413 PMC3020287
  11. [11]Berry CM Hertzog PJ Mangan NE Interferons as biomarkers and effectors: lessons learned from animal models Biomark Med 2012 6 159 176 22448790
  12. [12]De Weerd NA Nguyen T The interferons and their receptors – distribution and regulation Immunol Cell Biol 2012 90 483 491 22410872 PMC7165917
  13. [13]Platanias LC Mechanisms of type-I- and type-II-interferon-mediated signalling Nat Rev Immunol 2005 5 375 386 15864272
  14. [14]Stark GR Darnell JEJ The JAK–STAT pathway at twenty Immunity 2012 36 503 514 22520844 PMC3909993
  15. [15]Wang BX Rahbar R Fish EN Interferon: current status and future prospects in cancer therapy J Interferon Cytokine Res 2011 31 545 552 21323567
  16. [16]Croze E Differential gene expression and translational approaches to identify biomarkers of interferon beta activity in multiple sclerosis J Interferon Cytokine Res 2010 30 743 749 20874251
  17. [17]Randall RE Goodbourn S Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures J Gen Virol 2008 89 1 47 18089727
  18. [18]Pitha PM Kunzi MS Type I interferon: the ever unfolding story Curr Top Microbiol Immunol 2007 316 41 70 17969443
  19. [19]Uze G Schreiber G Piehler J Pellegrini S The receptor of the type I interferon family Curr Top Microbiol Immunol 2007 316 71 95 17969444
  20. [20]Rani MR Foster GR Leung S Leaman D Stark GR Characterization of beta-R1, a gene that is selectively induced by interferon-beta (IFN-beta) compared with IFN-alpha J Biol Chem 1996 271 22878 22884 8798467
  21. [21]Abramovich C Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-alpha and IFN-beta EMBO J 1994 13 5871 5877 7813427 PMC395562
  22. [22]Platanias LC Uddin S Domanski P Colamonici OR Differences in interferon alpha and beta signaling. Interferon beta selectively induces the interaction of the alpha and betaL subunits of the type I interferon receptor J Biol Chem 1996 271 23630 23633 8798579
  23. [23]Russell-Harde D Wagner TC Perez HD Croze E Formation of a uniquely stable type I interferon receptor complex by interferon beta is dependent upon particular interactions between interferon beta and its receptor and independent of tyrosine phosphorylation Biochem Biophys Res Commun 1999 255 539 544 10049744
  24. [24]Foster GR IFN-alpha subtypes differentially affect human T cell motility J Immunol 2004 173 1663 1670 15265895
  25. [25]Kalinke U Prinz M Endogenous, or therapeutically induced, type I interferon responses differentially modulate Th1/Th17-mediated autoimmunity in the CNS Immunol Cell Biol 2012 90 505 509 22430251 PMC3365287
  26. [26]Marijanovic Z Ragimbeau J Van der Heyden J Uze G Pellegrini S Comparable potency of IFNalpha2 and IFNbeta on immediate JAK/STAT activation but differential down- regulation of IFNAR2 Biochem J 2007 407 141 151 17627610 PMC2267396
  27. [27]Jaks E Gavutis M Uze G Martal J Piehler J Differential receptor subunit affinities of type I interferons govern differential signal activation J Mol Biol 2007 366 525 539 17174979
  28. [28]Langer JA Interferon at 50: new molecules, new potential, new (and old) questions Sci STKE 2007 2007 pe53 17895481
  29. [29]Severa M Differential responsiveness to IFN-alpha and IFN-beta of human mature DC through modulation of IFNAR expression J Leukoc Biol 2006 79 1286 1294 16624932
  30. [30]Brierley MM Fish EN Review: IFN-alpha/beta receptor interactions to biologic outcomes: understanding the circuitry J Interferon Cytokine Res 2002 22 835 845 12396722
  31. [31]Jaitin DA Inquiring into the differential action of interferons (IFNs): an IFN-alpha2 mutant with enhanced affinity to IFNAR1 is functionally similar to IFN-beta Mol Cell Biol 2006 26 1888 1897 16479007 PMC1430259
  32. [32]Thomas C Structural linkage between ligand discrimination and receptor activation by type I interferons Cell 2011 146 621 632 21854986 PMC3166218
  33. [33]Van Boxel-Dezaire AH Zula JA Xu Y Ransohoff RM Jacobberger JW Stark GR Major differences in the responses of primary human leukocyte subsets to IFN-beta J Immunol 2010 185 5888 5899 20956346 PMC3244975
  34. [34]Jaitin DA Schreiber G Upregulation of a small subset of genes drives type I interferon-induced antiviral memory J Interferon Cytokine Res 2007 27 653 664 17784817
  35. [35]Cheon H Stark GR Unphosphorylated STAT1 prolongs the expression of interferon-induced immune regulatory genes Proc Natl Acad Sci USA 2009 106 9373 9378 19478064 PMC2688000
  36. [36]Der SD Zhou A Williams BR Silverman RH Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays Proc Natl Acad Sci USA 1998 95 15623 15628 9861020 PMC28094
  37. [37]De Veer MJ Functional classification of interferon-stimulated genes identified using microarrays J Leukoc Biol 2001 69 912 920 11404376
  38. [38]Kalie E Jaitin DA Podoplelova Y Piehler J Schreiber G The stability of the ternary interferon–receptor complex rather than the affinity to the individual subunits dictates differential biological activities J Biol Chem 2008 283 32925 32936 18801736
  39. [39]Piehler J Roisman LC Schreiber G New structural and functional aspects of the type I interferon–receptor interaction revealed by comprehensive mutational analysis of the binding interface J Biol Chem 2000 275 40425 40433 10984492
  40. [40]Levin D Harari D Schreiber G Stochastic receptor expression determines cell fate upon interferon treatment Mol Cell Biol 2011 31 3252 3266 21690295 PMC3147786
  41. [41]Leaman DW Novel growth and death related interferon-stimulated genes (ISGs) in melanoma: greater potency of IFN-beta compared with IFN-alpha2 J Interferon Cytokine Res 2003 23 745 756 14769151
  42. [42]Samarajiwa SA Forster S Auchettl K Hertzog PJ INTERFEROME: the database of interferon regulated genes Nucleic Acids Res 2009 37 D852 D857 18996892 PMC2686605
  43. [43]Coelho LF De Freitas Almeida GM Mennechet FJ Blangy A Uze G Interferon-{alpha} and -{beta} differentially regulate osteoclastogenesis: role of differential induction of chemokine CXCL11 expression Proc Natl Acad Sci USA 2005 102 11917 11922 16081539 PMC1187968
  44. [44]Schoggins JW Rice CM Interferon-stimulated genes and their antiviral effector functions Curr Opin Virol 2011 1 519 525 22328912 PMC3274382
  45. [45]Kotenko SV Langer JA Full house: 12 receptors for 27 cytokines Int Immunopharmacol 2004 4 593 608 15120645
  46. [46]Senda T Three-dimensional crystal structure of recombinant murine interferon-b EMBO J 1992 11 3193 1505514 PMC556852
  47. [47]Radhakrishnan R Zinc mediated dimer of human interferon-alpha 2b revealed by X-ray crystallography Structure 1996 4 1453 1463 8994971
  48. [48]Klaus W Gsell B Labhardt AM Wipf B Senn H The three-dimensional high resolution structure of human interferon alpha-2a determined by heteronuclear NMR spectroscopy in solution J Mol Biol 1997 274 661 675 9417943
  49. [49]Karpusas M Nolte M Benton CB Meier W Lipscomb WN Goelz S The crystal structure of human interferon beta at 2.2-A resolution Proc Natl Acad Sci USA 1997 94 11813 11818 9342320 PMC23607
  50. [50]Chill JH Quadt SR Levy R Schreiber G Anglister J The human type I interferon receptor: NMR structure reveals the molecular basis of ligand binding Structure 2003 11 791 802 12842042
  51. [51]Roisman LC Piehler J Trosset JY Scheraga HA Schreiber G Structure of the interferon–receptor complex determined by distance constraints from double-mutant cycles and flexible docking Proc Natl Acad Sci USA 2001 98 13231 13236 11698684 PMC60853
  52. [52]Akabayov SR Biron Z Lamken P Piehler J Anglister J NMR mapping of the IFNAR1-EC binding site on IFNalpha2 reveals allosteric changes in the IFNAR2-EC binding site Biochemistry 2010 49 687 695 20047337 PMC2827818
  53. [53]Li Z Strunk JJ Lamken P Piehler J Walz T The EM structure of a type I interferon–receptor complex reveals a novel mechanism for cytokine signaling J Mol Biol 2008 377 715 724 18252254 PMC2577817
  54. [54]Strunk JJ Ligand binding induces a conformational change in ifnar1 that is propagated to its membrane-proximal domain J Mol Biol 2008 377 725 739 18294654
  55. [55]Bleicher L Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism FEBS Lett 2008 582 2985 2992 18675809
  56. [56]Jones BC Logsdon NJ Walter MR Structure of IL-22 bound to its high-affinity IL-22R1 chain Structure 2008 16 1333 1344 18599299 PMC2637415
  57. [57]Josephson K Logsdon NJ Walter MR Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site Immunity 2001 15 35 46 11485736
  58. [58]Walter MR Crystal structure of a complex between interferon-gamma and its soluble high-affinity receptor Nature 1995 376 230 235 7617032
  59. [59]Miknis ZJ Magracheva E Li W Zdanov A Kotenko SV Wlodawer A Crystal structure of human interferon-lambda1 in complex with its high-affinity receptor interferon-lambdaR1 J Mol Biol 2010 404 650 664 20934432 PMC2991516
  60. [60]Roisman LC Jaitin DA Baker DP Schreiber G Mutational analysis of the IFNAR1 binding site on IFNalpha2 reveals the architecture of a weak ligand-receptor binding-site J Mol Biol 2005 353 271 281 16171819
  61. [61]Lamken P Gavutis M Peters I Van der Heyden J Uze G Piehler J Functional cartography of the ectodomain of the type I interferon receptor subunit ifnar1 J Mol Biol 2005 350 476 488 15946680
  62. [62]Runkel L Systematic mutational mapping of sites on human interferon-b-1a that are important for receptor binding and functional activity Biochemistry 2000 39 2538 2551 10704203
  63. [63]Peleg-Shulman T Roisman LC Zupkovitz G Schreiber G Optimizing the binding affinity of a carrier protein: a case study on the interaction between soluble ifnar2 and interferon {beta} J Biol Chem 2004 279 18046 18053 14960565
  64. [64]Slutzki M Jaitin DA Yehezkel TB Schreiber G Variations in the unstructured C-terminal tail of interferons contribute to differential receptor binding and biological activity J Mol Biol 2006 360 1019 1030 16815442
  65. [65]Krause CD Preassembly and ligand-induced restructuring of the chains of the IFN-gamma receptor complex: the roles of Jak kinases, Stat1 and the receptor chains Cell Res 2006 16 55 69 16467876
  66. [66]Brown RJ Model for growth hormone receptor activation based on subunit rotation within a receptor dimer Nat Struct Mol Biol 2005 12 814 821 16116438
  67. [67]Kubatzky KF Liu W Goldgraben K Simmerling C Smith SO Constantinescu SN Structural requirements of the extracellular to transmembrane domain junction for erythropoietin receptor function J Biol Chem 2005 280 14844 14854 15657048
  68. [68]Seubert N Active and inactive orientations of the transmembrane and cytosolic domains of the erythropoietin receptor dimer Mol Cell 2003 12 1239 1250 14636581
  69. [69]Lopez AF Molecular basis of cytokine receptor activation IUBMB Life 2010 62 509 518 20540154
  70. [70]Dagil R The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation: insight from structures of the prolactin receptor Structure 2012 20 270 282 22325776
  71. [71]Strunk JJ Probing protein conformations by in situ non-covalent fluorescence labeling Bioconjug Chem 2008 20 41 46 19102695
  72. [72]Whitty A Interaction affinity between cytokine receptor components on the cell surface Proc Natl Acad Sci USA 1998 95 13165 13170 9789059 PMC23746
  73. [73]Lavoie TB Binding and activity of all human alpha interferon subtypes Cytokine 2011 56 282 289 21856167
  74. [74]Piehler J Schreiber G Fast transient cytokine–receptor interactions monitored in real-time by reflectometric interference spectroscopy Anal Biochem 2001 289 173 186 11161311
  75. [75]Lamken P Lata S Gavutis M Piehler J Ligand-induced assembling of the type I interferon receptor on supported lipid bilayers J Mol Biol 2004 341 303 318 15312780
  76. [76]Moraga I Harari D Schreiber G Uze G Pellegrini S Receptor density is key to the alpha2/beta interferon differential activities Mol Cell Biol 2009 29 4778 4787 19564411 PMC2725717
  77. [77]Piehler J Schreiber G Biophysical analysis of the interaction of human ifnar2 expressed in E. coli with IFNalpha2 J Mol Biol 1999 289 57 67 10339405
  78. [78]Gavutis M Lata S Piehler J Probing 2-dimensional protein–protein interactions on model membranes Nat Protoc 2006 1 2091 2103 17487200
  79. [79]Yamamoto K Creation of interferon-alpha8 (IFN-alpha8) mutants with amino acid substitutions against IFN-alpha receptor-2 (IFNAR-2)-binding sites using phage display system and evaluation of their biologic properties J Interferon Cytokine Res 2009 29 161 170 19196068
  80. [80]Pan M Kalie E Scaglione BJ Raveche ES Schreiber G Langer JA Mutation of the IFNAR-1 receptor binding site of human IFN-alpha2 generates type I IFN competitive antagonists Biochemistry 2008 47 12018 12027 18937499
  81. [81]Kalie E Jaitin DA Abramovich R Schreiber G An interferon {alpha}2 mutant optimized by phage display for IFNAR1 binding confers specifically enhanced antitumor activities J Biol Chem 2007 282 11602 11611 17310065
  82. [82]Piehler J Schreiber G Mutational and structural analysis of the binding interface between type I interferons and their receptor ifnar2 J Mol Biol 1999 294 223 237 10556041
  83. [83]Dubois A Enhanced anti-HCV activity of interferon alpha 17 subtype Virol J 2009 6 70 19493343 PMC2697159
  84. [84]Vazquez N Schmeisser H Dolan MA Bekisz J Zoon KC Wahl SM Structural variants of IFNalpha preferentially promote antiviral functions Blood 2011 118 2567 2577 21757613 PMC3167361
  85. [85]Manry J Evolutionary genetic dissection of human interferons J Exp Med 2011 208 2747 2759 22162829 PMC3244034
  86. [86]Wagner TC Interferon receptor expression regulates the antiproliferative effects of interferons on cancer cells and solid tumors Int J Cancer 2004 111 32 42 15185340
  87. [87]Gavutis M Lata S Lamken P Muller P Piehler J Lateral ligand–receptor interactions on membranes probed by simultaneous fluorescence-interference detection Biophys J 2005 88 4289 4302 15778442 PMC1305658
  88. [88]Lata S Gavutis M Piehler J Monitoring the dynamics of ligand–receptor complexes on model membranes J Am Chem Soc 2006 128 6 7 16390094
  89. [89]Gavutis M Jaks E Lamken P Piehler J Determination of the two-dimensional interaction rate constants of a cytokine receptor complex Biophys J 2006 90 3345 3355 16473899 PMC1432116
  90. [90]Kusumi A Membrane mechanisms for signal transduction: the coupling of the mesoscale raft domains to membrane-skeleton-induced compartments and dynamic protein complexes Semin Cell Dev Biol 2012 23 126 144 22309841
  91. [91]You C Self-controlled monofunctionalization of quantum dots for multiplexed protein tracking in live cells Angew Chem Int Ed Engl 2010 49 4108 4112 20432494
  92. [92]Kusumi A Paradigm shift of the plasma membrane concept from the two-dimensional continuum fluid to the partitioned fluid: high-speed single-molecule tracking of membrane molecules Annu Rev Biophys Biomol Struct 2005 34 351 378 15869394
  93. [93]Kumar KG Basal ubiquitin-independent internalization of interferon alpha receptor is prevented by Tyk2-mediated masking of a linear endocytic motif J Biol Chem 2008 283 18566 18572 18474601 PMC2441555
  94. [94]Kumar KG Krolewski JJ Fuchs SY Phosphorylation and specific ubiquitin acceptor sites are required for ubiquitination and degradation of the IFNAR1 subunit of type I interferon receptor J Biol Chem 2004 279 46614 46620 15337770
  95. [95]Kumar KG Tang W Ravindranath AK Clark WA Croze E Fuchs SY SCF(HOS) ubiquitin ligase mediates the ligand-induced down-regulation of the interferon-alpha receptor EMBO J 2003 22 5480 5490 14532120 PMC213778
  96. [96]Zheng H Qian J Varghese B Baker DP Fuchs S Ligand-stimulated downregulation of the alpha interferon receptor: role of protein kinase D2 Mol Cell Biol 2011 31 710 720 21173164 PMC3028644
  97. [97]Kumar KG Site-specific ubiquitination exposes a linear motif to promote interferon-{alpha} receptor endocytosis J Cell Biol 2007 179 935 950 18056411 PMC2099190
  98. [98]Marchetti M Stat-mediated signaling induced by type I and type II interferons (IFNs) is differentially controlled through lipid microdomain association and clathrin-dependent endocytosis of IFN receptors Mol Biol Cell 2006 17 2896 2909 16624862 PMC1483027
  99. [99]Marijanovic Z Ragimbeau J Kumar KG Fuchs SY Pellegrini S TYK2 activity promotes ligand-induced IFNAR1 proteolysis Biochem J 2006 397 31 38 16551269 PMC1479745
  100. [100]Piganis RA Suppressor of cytokine signaling (SOCS) 1 inhibits type I interferon (IFN) signaling via the interferon alpha receptor (IFNAR1)-associated tyrosine kinase Tyk2 J Biol Chem 2011 286 33811 33818 21757742 PMC3190811
  101. [101]Payelle-Brogard B Pellegrini S Biochemical monitoring of the early endocytic traffic of the type I interferon receptor J Interferon Cytokine Res 2010 30 89 98 20028207
  102. [102]Fuchs SY Ubiquitination-mediated regulation of interferon responses Growth Factors 2012 30 141 148 22394219 PMC3703147
  103. [103]Dupont SA Goelz S Goyal J Green M Mechanisms for regulation of cellular responsiveness to human IFN-beta1a J Interferon Cytokine Res 2002 22 491 501 12034032
  104. [104]Malakhov MP Malakhova OA Kim KI Ritchie KJ Zhang DE UBP43 (USP18) specifically removes ISG15 from conjugated proteins J Biol Chem 2002 277 9976 9981 11788588
  105. [105]Zhang D Zhang DE Interferon-stimulated gene 15 and the protein ISGylation system J Interferon Cytokine Res 2011 31 119 130 21190487 PMC3021351
  106. [106]Ritchie KJ Role of ISG15 protease UBP43 (USP18) in innate immunity to viral infection Nat Med 2004 10 1374 1378 15531891
  107. [107]Malakhova OA UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity EMBO J 2006 25 2358 2367 16710296 PMC1478183
  108. [108]Francois-Newton V USP18-based negative feedback control is induced by type I and type III interferons and specifically inactivates interferon alpha response PLoS ONE 2011 6 e22200 21779393 PMC3136508

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Authors
Piehler, J., Thomas, C., Garcia, K. C., & Schreiber, G.
Affiliations
  • Osnabrück University (DE)
  • Howard Hughes Medical Institute (US)
  • Departments of Molecular and Cellular Physiology, and Structural Biology Howard Hughes Medical Institute Stanford University School of Medicine Stanford CA USA
  • Weizmann Institute of Science (IL)
Corresponding author
Schreiber, Gideon
ORCID
Venue
Immunological Reviews
Publisher
Wiley
Published
2012-10-10
Volume
250
Issue
1
Pages
317-334
ISSN
  • 0105-2896 (ISSN-L)
  • 1600-065X
DOI
10.1111/imr.12001
PMC
PMC3986811
OpenAlex
W2107031229
Cited by
230
References
0
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FWCI
1.36
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Immunological Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R37AI051321, R01AI051321)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
type I interferon, interferon receptor, receptor assembly, ternary complex, receptor dimerization, ligand binding affinity, endocytosis, negative feedback, receptor trafficking, innate immunity, cytokine signaling
MeSH terms
Binding Sites, Endocytosis, Humans, Interferon Type I, Models, Molecular, Protein Binding, T-Lymphocytes, Thermodynamics, Signal Transduction, Protein Structure, Tertiary, Protein Subunits, Feedback, Physiological, Receptor, Interferon alpha-beta, Protein Multimerization

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