Structural principles of tumor necrosis factor superfamily signaling
Gloss
Tumor necrosis factor (TNF) superfamily pathways regulate cell proliferation, cell death, and morphogenesis. TNF superfamily receptors mediate various cancers and immune-mediated diseases. Understanding of the mechanisms of TNF superfamily signaling and the structure and geometry of ligands, receptors, and their interactions is essential to designing effective agonist and antagonist drugs. In this review, consisting of four figures, one table, and 96 references, we discuss our current understanding of TNF ligand-receptor conformations and how this informs signaling and the design of current and prospective therapeutics.
Abstract
The tumor necrosis factor (TNF) ligand and receptor superfamilies play an important role in cell proliferation, survival, and death. Stimulating or inhibiting TNF superfamily signaling pathways is expected to have therapeutic benefit for patients with various diseases, including cancer, autoimmunity, and infectious diseases. We review our current understanding of the structure and geometry of TNF superfamily ligands, receptors, and their interactions. A trimeric ligand and three receptors, each binding at the interface of two ligand monomers, form the basic unit of signaling. Clustering of multiple receptor subunits is necessary for efficient signaling. Current reports suggest that the receptors are prearranged on the cell surface in a “nonsignaling,” resting state in a large hexagonal structure of antiparallel dimers. Receptor activation requires ligand binding, and cross-linking antibodies can stabilize the receptors, thereby maintaining the active, signaling state. On the other hand, an antagonist antibody that locks receptor arrangement in antiparallel dimers effectively blocks signaling. This model may aid the design of more effective TNF signaling–targeted therapies.
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REFERENCES AND NOTES
1
B. B. Aggarwal, Signalling pathways of the TNF superfamily: A double-edged sword. Nat. Rev. Immunol. 3, 745–756 (2003).
2
R. M. Locksley, N. Killeen, M. J. Lenardo, The TNF and TNF receptor superfamilies: Integrating mammalian biology. Cell 104, 487–501 (2001).
3
J.-L. Bodmer, P. Schneider, J. Tschopp, The molecular architecture of the TNF superfamily. Trends Biochem. Sci. 27, 19–26 (2002).
4
E. Bremer, Targeting of the tumor necrosis factor receptor superfamily for cancer immunotherapy. ISRN Oncol. 2013, 371854 (2013).
5
X. Chen, M. Bäumel, D. N. Männel, O. M. Z. Howard, J. J. Oppenheim, Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells. J. Immunol. 179, 154–161 (2007).
6
D. X. Nguyen, M. R. Ehrenstein, Anti-TNF drives regulatory T cell expansion by paradoxically promoting membrane TNF–TNF-RII binding in rheumatoid arthritis. J. Exp. Med. 213, 1241–1253 (2016).
7
Y. Okubo, T. Mera, L. Wang, D. L. Faustman, Homogeneous expansion of human T-regulatory cells via tumor necrosis factor receptor 2. Sci. Rep. 3, 3153 (2013).
8
M. J. Eck, S. R. Sprang, The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding. J. Biol. Chem. 264, 17595–17605 (1989).
9
H. T. Idriss, J. H. Naismith, TNFα and the TNF receptor superfamily: Structure-function relationship(s). Microsc. Res. Tech. 50, 184–195 (2000).
10
S. W. Fesik, Insights into programmed cell death through structural biology. Cell 103, 273–282 (2000).
11
M. J. Eck, M. Ultsch, E. Rinderknecht, A. M. de Vos, S. R. Sprang, The structure of human lymphotoxin (tumor necrosis factor-beta) at 1.9-A resolution. J. Biol. Chem. 267, 2119–2122 (1992).
12
J. Sudhamsu, J. Yin, E. Y. Chiang, M. A. Starovasnik, J. L. Grogan, S. G. Hymowitz, Dimerization of LTβR by LTα1β2 is necessary and sufficient for signal transduction. Proc. Natl. Acad. Sci. U.S.A. 110, 19896–19901 (2013).
13
E.-Y. Won, K. Cha, J.-S. Byun, D.-U. Kim, S. Shin, B. Ahn, Y. H. Kim, A. J. Rice, T. Walz, B. S. Kwon, H.-S. Cho, The structure of the trimer of human 4-1BB ligand is unique among members of the tumor necrosis factor superfamily. J. Biol. Chem. 285, 9202–9210 (2010).
14
M. Karpusas, Y.-M. Hsu, J.-h. Wang, J. Thompson, S. Lederman, L. Chess, D. Thomas, 2 å crystal structure of an extracellular fragment of human CD40 ligand. Structure 3, 1031–1039 (1995).
15
C. Zhan, Q. Yan, Y. Patskovsky, Z. Li, R. Toro, A. Meyer, H. Cheng, M. Brenowitz, S. G. Nathenson, S. C. Almo, Biochemical and structural characterization of the human TL1A ectodomain. Biochemistry 48, 7636–7645 (2009).
16
S. G. Hymowitz, M. P. O’Connell, M. H. Ultsch, A. Hurst, K. Totpal, A. Ashkenazi, A. M. de Vos, R. F. Kelley, A unique zinc-binding site revealed by a high-resolution X-ray structure of homotrimeric Apo2L/TRAIL. Biochemistry 39, 633–640 (2000).
17
D. M. Compaan, S. G. Hymowitz, The crystal structure of the costimulatory OX40-OX40L complex. Structure 14, 1321–1330 (2006).
18
J. Lam, C. A. Nelson, F. P. Ross, S. L. Teitelbaum, D. H. Fremont, Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity. J. Clin. Invest. 108, 971–979 (2001).
19
S. G. Hymowitz, D. R. Patel, H. J. A. Wallweber, S. Runyon, M. Yan, J. Yin, S. K. Shriver, N. C. Gordon, B. Pan, N. J. Skelton, R. F. Kelley, M. A. Starovasnik, Structures of APRIL-receptor complexes: Like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding. J. Biol. Chem. 280, 7218–7227 (2005).
20
W. Liu, C. Zhan, H. Cheng, P. R. Kumar, J. B. Bonanno, S. G. Nathenson, S. C. Almo, Mechanistic basis for functional promiscuity in the TNF and TNF receptor superfamilies: Structure of the LIGHT:DcR3 assembly. Structure 22, 1252–1262 (2014).
21
C. Liu, T. S. Walter, P. Huang, S. Zhang, X. Zhu, Y. Wu, L. R. Wedderburn, P. Tang, R. J. Owens, D. I. Stuart, J. Ren, B. Gao, Structural and functional insights of RANKL-RANK interaction and signaling. J. Immunol. 184, 6910–6919 (2010).
22
S.-S. Cha, M.-S. Kim, Y. H. Choi, B.-J. Sung, N. K. Shin, H.-C. Shin, Y. C. Sung, B.-H. Oh, 2.8 A resolution crystal structure of human TRAIL, a cytokine with selective antitumor activity. Immunity 11, 253–261 (1999).
23
T. Jin, F. Guo, S. Kim, A. Howard, Y.-Z. Zhang, X-ray crystal structure of TNF ligand family member TL1A at 2.1 Å. Biochem. Biophys. Res. Commun. 364, 1–6 (2007).
24
H. J. A. Wallweber, D. M. Compaan, M. A. Starovasnik, S. G. Hymowitz, The crystal structure of a proliferation-inducing ligand, APRIL. J. Mol. Biol. 343, 283–290 (2004).
25
Y. Liu, L. Xu, N. Opalka, J. Kappler, H.-B. Shu, G. Zhang, Crystal structure of sTALL-1 reveals a virus-like assembly of TNF family ligands. Cell 108, 383–394 (2002).
26
M. Karpusas, T. G. Cachero, F. Qian, A. Boriack-Sjodin, C. Mullen, K. Strauch, Y.-M. Hsu, S. L. Kalled, Crystal structure of extracellular human BAFF, a TNF family member that stimulates B lymphocytes. J. Mol. Biol. 315, 1145–1154 (2002).
27
D. A. Oren, Y. Li, Y. Volovik, T. S. Morris, C. Dharia, K. Das, O. Galperina, R. Gentz, E. Arnold, Structural basis of BLyS receptor recognition. Nat. Struct. Biol. 9, 288–292 (2002).
28
S. G. Hymowitz, D. M. Compaan, M. Yan, H. J. A. Wallweber, V. M. Dixit, M. A. Starovasnik, A. M. de Vos, The crystal structures of EDA-A1 and EDA-A2: Splice variants with distinct receptor specificity. Structure 11, 1513–1520 (2003).
29
K. Chattopadhyay, U. A. Ramagopal, A. Mukhopadhaya, V. N. Malashkevich, T. P. Dilorenzo, M. Brenowitz, S. G. Nathenson, S. C. Almo, Assembly and structural properties of glucocorticoid-induced TNF receptor ligand: Implications for function. Proc. Natl. Acad. Sci. U.S.A. 104, 19452–19457 (2007).
30
K. Chattopadhyay, U. A. Ramagopal, M. Brenowitz, S. G. Nathenson, S. C. Almo, Evolution of GITRL immune function: Murine GITRL exhibits unique structural and biochemical properties within the TNF superfamily. Proc. Natl. Acad. Sci. U.S.A. 105, 635–640 (2008).
31
D. W. Banner, A. D’Arcy, W. Janes, R. Gentz, H.-J. Schoenfeld, C. Broger, H. Loetscher, W. Lesslauer, Crystal structure of the soluble human 55 kd TNF receptor-human TNFβ complex: Implications for TNF receptor activation. Cell 73, 431–445 (1993).
32
J. Mongkolsapaya, J. M. Grimes, N. Chen, X.-N. Xu, D. I. Stuart, E. Y. Jones, G. R. Screaton, Structure of the TRAIL–DR5 complex reveals mechanisms conferring specificity in apoptotic initiation. Nat. Struct. Biol. 6, 1048–1053 (1999).
33
S. G. Hymowitz, H. W. Christinger, G. Fuh, M. Ultsch, M. O’Connell, R. F. Kelley, A. Ashkenazi, A. M. de Vos, Triggering cell death: The crystal structure of Apo2L/TRAIL in a complex with death receptor 5. Mol. Cell 4, 563–571 (1999).
34
Y. Mukai, T. Nakamura, M. Yoshikawa, Y. Yoshioka, S.-i. Tsunoda, S. Nakagawa, Y. Yamagata, Y. Tsutsumi, Solution of the structure of the TNF-TNFR2 complex. Sci. Signal. 3, ra83 (2010).
35
H.-J. An, Y. J. Kim, D. H. Song, B. S. Park, H. M. Kim, J. D. Lee, S.-G. Paik, J.-O. Lee, H. Lee, Crystallographic and mutational analysis of the CD40-CD154 complex and its implications for receptor activation. J. Biol. Chem. 286, 11226–11235 (2011).
36
S.-S. Cha, B.-J. Sung, Y.-A. Kim, Y.-L. Song, H.-J. Kim, S. Kim, M.-S. Lee, B.-H. Oh, Crystal structure of TRAIL-DR5 complex identifies a critical role of the unique frame insertion in conferring recognition specificity. J. Biol. Chem. 275, 31171–31177 (2000).
37
X. Luan, Q. Lu, Y. Jiang, S. Zhang, Q. Wang, H. Yuan, W. Zhao, J. Wang, X. Wang, Crystal structure of human RANKL complexed with its decoy receptor osteoprotegerin. J. Immunol. 189, 245–252 (2012).
38
C. Zhan, Y. Patskovsky, Q. Yan, Z. Li, U. Ramagopal, H. Cheng, M. Brenowitz, X. Hui, S. G. Nathenson, S. C. Almo, Decoy strategies: The structure of TL1A:DcR3 complex. Structure 19, 162–171 (2011).
39
Y. Liu, X. Hong, J. Kappler, L. Jiang, R. Zhang, L. Xu, C.-H. Pan, W. E. Martin, R. C. Murphy, H.-B. Shu, S. Dai, G. Zhang, Ligand–receptor binding revealed by the TNF family member TALL-1. Nature 423, 49–56 (2003).
40
H. M. Kim, K. S. Yu, M. E. Lee, D. R. Shin, Y. S. Kim, S.-G. Paik, O. J. Yoo, H. Lee, J.-O. Lee, Crystal structure of the BAFF–BAFF-R complex and its implications for receptor activation. Nat. Struct. Biol. 10, 342–348 (2003).
41
J. H. Naismith, T. Q. Devine, B. J. Brandhuber, S. R. Sprang, Crystallographic evidence for dimerization of unliganded tumor necrosis factor receptor. J. Biol. Chem. 270, 13303–13307 (1995).
42
K. Peppel, D. Crawford, B. Beutler, A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity. J. Exp. Med. 174, 1483–1489 (1991).
43
H. Torrey, J. Butterworth, T. Mera, Y. Okubo, L. Wang, D. Baum, A. Defusco, S. Plager, S. Warden, D. Huang, E. Vanamee, R. Foster, D. L. Faustman, Targeting TNFR2 with antagonistic antibodies inhibits proliferation of ovarian cancer cells and tumor-associated Tregs. Sci. Signal. 10, eaaf8606 (2017).
44
L. M. Sedger, S. R. Osvath, X.-M. Xu, G. Li, F. K.-M. Chan, J. W. Barrett, G. McFadden, Poxvirus tumor necrosis factor receptor (TNFR)-like T2 proteins contain a conserved preligand assembly domain that inhibits cellular TNFR1-induced cell death. J. Virol. 80, 9300–9309 (2006).
45
G. Papoff, P. Hausler, A. Eramo, M. G. Pagano, G. Di Leve, A. Signore, G. Ruberti, Identification and characterization of a ligand-independent oligomerization domain in the extracellular region of the CD95 death receptor. J. Biol. Chem. 274, 38241–38250 (1999).
46
F. K.-M. Chan, H. J. Chun, L. Zheng, R. M. Siegel, K. L. Bui, M. J. Lenardo, A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science 288, 2351–2354 (2000).
47
R. M. Siegel, J. K. Frederiksen, D. A. Zacharias, F. K.-M. Chan, M. Johnson, D. Lynch, R. Y. Tsien, M. J. Lenardo, Fas preassociation required for apoptosis signaling and dominant inhibition by pathogenic mutations. Science 288, 2354–2357 (2000).
48
L. Clancy, K. Mruk, K. Archer, M. Woelfel, J. Mongkolsapaya, G. Screaton, M. J. Lenardo, F. K.-M. Chan, Preligand assembly domain-mediated ligand-independent association between TRAIL receptor 4 (TR4) and TR2 regulates TRAIL-induced apoptosis. Proc. Natl. Acad. Sci. U.S.A. 102, 18099–18104 (2005).
49
S. Neumann, J. Hasenauer, N. Pollak, P. Scheurich, Dominant negative effects of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor 4 on TRAIL receptor 1 signaling by formation of heteromeric complexes. J. Biol. Chem. 289, 16576–16587 (2014).
50
H. Walczak, R. E. Miller, K. Ariail, B. Gliniak, T. S. Griffith, M. Kubin, W. Chin, J. Jones, A. Woodward, T. Le, C. Smith, P. Smolak, R. G. Goodwin, C. T. Rauch, J. C. L. Schuh, D. H. Lynch, Tumoricidal activity of tumor necrosis factor–related apoptosis–inducing ligand in vivo. Nat. Med. 5, 157–163 (1999).
51
A. Ashkenazi, R. C. Pai, S. Fong, S. A. Leung, D. A. Lawrence, S. A. Marsters, C. Blackie, L. Chang, A. E. McMurtrey, A. Hebert, L. DeForge, I. L. Koumenis, D. Lewis, L. Harris, J. Bussiere, H. Koeppen, Z. Shahrokh, R. H. Schwall, Safety and antitumor activity of recombinant soluble Apo2 ligand. J. Clin. Invest. 104, 155–162 (1999).
52
G. Pan, K. O’Rourke, A. M. Chinnaiyan, R. Gentz, R. Ebner, J. Ni, V. M. Dixit, The receptor for the cytotoxic ligand TRAIL. Science 276, 111–113 (1997).
53
P. M. Chaudhary, M. Eby, A. Jasmin, A. Bookwalter, J. Murray, L. Hood, Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-κB pathway. Immunity 7, 821–830 (1997).
54
S. A. Marsters, J. P. Sheridan, R. M. Pitti, A. Huang, M. Skubatch, D. Baldwin, J. Yuan, A. Gurney, A. D. Goddard, P. Godowski, A. Ashkenazi, A novel receptor for Apo2L/TRAIL contains a truncated death domain. Curr. Biol. 7, 1003–1006 (1997).
55
D. Wallach, M. Boldin, E. Varfolomeev, R. Beyaert, P. Vandenabeele, F. Wiers, Cell death induction by receptors of the TNF family: Towards a molecular understanding. FEBS Lett. 410, 96–106 (1997).
56
J. G. Emery, P. McDonnell, M. B. Burke, K. C. Deen, S. Lyn, C. Silverman, E. Dul, E. R. Appelbaum, C Eichman, R. DiPrinzio, R. A. Dodds, I. E. James, M. Rosenberg, J. C. Lee, P. R. Young, Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J. Biol. Chem. 273, 14363–14367 (1998).
57
A. Corti, G. Fassina, F. Marcucci, E. Barbanti, G. Cassani, Oligomeric tumour necrosis factor α slowly converts into inactive forms at bioactive levels. Biochem. J. 284 (Pt. 3), 905–910 (1992).
58
J.-L. Bodmer, P. Meier, J. Tschopp, P. Schneider, Cysteine 230 is essential for the structure and activity of the cytotoxic ligand TRAIL. J. Biol. Chem. 275, 20632–20637 (2000).
59
S. K. Kelley, L. A. Harris, D. Xie, L. Deforge, K. Totpal, J. Bussiere, J. A. Fox, Preclinical studies to predict the disposition of Apo2L/tumor necrosis factor-related apoptosis-inducing ligand in humans: Characterization of in vivo efficacy, pharmacokinetics, and safety.J. Pharmacol. Exp. Ther. 299, 31–38 (2001).
60
D. de Miguel, J. Lemke, A. Anel, H. Walczak, L. Martinez-Lostao, Onto better TRAILs for cancer treatment. Cell Death Differ. 23, 733–747 (2016).
61
M. Siegemund, N. Pollak, O. Seifert, K. Wahl, K. Hanak, A. Vogel, A. K. Nussler, D. Göttsch, S. Münkel, H. Bantel, R. E. Kontermann, K. Pfizenmaier, Superior antitumoral activity of dimerized targeted single-chain TRAIL fusion proteins under retention of tumor selectivity. Cell Death Dis. 3, e295 (2012).
62
T. M. Ganten, R. Koschny, J. Sykora, H. Schulze-Bergkamen, P. Buchler, T. L. Haas, M. B. Schader, A. Untergasser, W. Stremmel, H. Walczak, Preclinical differentiation between apparently safe and potentially hepatotoxic applications of TRAIL either alone or in combination with chemotherapeutic drugs. Clin. Cancer Res. 12, 2640–2646 (2006).
63
D. Berg, M. Lehne, N. Muller, D. Siegmund, S. Münkel, W. Sebald, K. Pfizenmaier, H. Wajant, Enforced covalent trimerization increases the activity of the TNF ligand family members TRAIL and CD95L. Cell Death Differ. 14, 2021–2034 (2007).
64
D. V. Rozanov, A. Y. Savinov, V. S. Golubkov, O. L. Rozanova, T. I. Postnova, E. A. Sergienko, S. Vasile, A. E. Aleshin, M. F. Rega, M. Pellecchia, A. Y. Strongin, Engineering a leucine zipper-TRAIL homotrimer with improved cytotoxicity in tumor cells. Mol. Cancer Ther. 8, 1515–1525 (2009).
65
B. Schneider, S. Münkel, A. Krippner-Heidenreich, I. Grunwald, W. S. Wels, H. Wajant, K. Pfizenmaier, J. Gerspach, Potent antitumoral activity of TRAIL through generation of tumor-targeted single-chain fusion proteins. Cell Death Dis. 1, e68 (2010).
66
R. S. Herbst, S. G. Eckhardt, R. Kurzrock, S. Ebbinghaus, P. J. O’Dwyer, M. S. Gordon, W. Novotny, M. A. Goldwasser, T. M. Tohnya, B. L. Lum, A. Ashkenazi, A. M. Jubb, D. S. Mendelson, Phase I dose-escalation study of recombinant human Apo2L/TRAIL, a dual proapoptotic receptor agonist, in patients with advanced cancer. J. Clin. Oncol. 28, 2839–2846 (2010).
67
J.-C. Soria, E. Smit, D. Khayat, B. Besse, X. Yang, C.-P. Hsu, D. Reese, J. Wiezorek, F. Blackhall, Phase 1b study of dulanermin (recombinant human Apo2L/TRAIL) in combination with paclitaxel, carboplatin, and bevacizumab in patients with advanced non-squamous non-small-cell lung cancer. J. Clin. Oncol. 28, 1527–1533 (2010).
68
H. L. Kindler, D. A. Richards, L. E. Garbo, E. B. Garon, J. J. Stephenson Jr., C. M. Rocha-Lima, H. Safran, D. Chan, D. M. Kocs, F. Galimi, J. McGreivy, S. L. Bray, Y. Hei, E. G. Feigal, E. Loh, C. S. Fuchs, A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer. Ann. Oncol. 23, 2834–2842 (2012).
69
L. Paz-Ares, B. Balint, R. H. de Boer, J. P. van Meerbeeck, R. Wierzbicki, P. De Souza, F. Galimi, V. Haddad, T. Sabin, Y.-j. Hei, Y. Pan, S. Cottrell, C.-P. Hsu, R. RamLau, A randomized phase 2 study of paclitaxel and carboplatin with or without conatumumab for first-line treatment of advanced non-small-cell lung cancer. J. Thorac. Oncol. 8, 329–337 (2013).
70
J. D. Graves, J. J. Kordich, T.-H. Huang, J. Piasecki, T. L. Bush, T. Sullivan, I. N. Foltz, W. Chang, H. Douangpanya, T. Dang, J. W. O’Neill, R. Mallari, X. Zhao, D. G. Branstetter, J. M. Rossi, A. M. Long, X. Huang, P. M. Holland, Apo2L/TRAIL and the death receptor 5 agonist antibody AMG 655 cooperate to promote receptor clustering and antitumor activity. Cancer Cell 26, 177–189 (2014).
71
M. H. Tuthill, A. Montinaro, J. Zinngrebe, K. Prieske, P. Draber, S. Prieske, T. Newsom-Davis, S. von Karstedt, J. Graves, H. Walczak, TRAIL-R2-specific antibodies and recombinant TRAIL can synergise to kill cancer cells. Oncogene 34, 2138–2144 (2015).
72
D. L. Faustman, M. Davis, TNF receptor 2 and disease: Autoimmunity and regenerative medicine. Front. Immunol. 4, 478 (2013).
73
F. L. Scott, B. Stec, C. Pop, M. K. Dobaczewska, J. J. Lee, E. Monosov, H. Robinson, G. S. Salvesen, R. Schwarzenbacher, S. J. Riedl, The Fas–FADD death domain complex structure unravels signalling by receptor clustering. Nature 457, 1019–1022 (2009).
74
J. R. McEntyre, T. J. Gibson, Patterns and clusters within the PSM column in TiBS, 1992–2004. Trends Biochem. Sci. 29, 627–633 (2004).
75
H. H. Park, Y.-C. Lo, S.-C. Lin, L. Wang, J. K. Yang, H. Wu, The death domain superfamily in intracellular signaling of apoptosis and inflammation. Annu. Rev. Immunol. 25, 561–586 (2007).
76
B. Huang, M. Eberstadt, E. T. Olejniczak, R. P. Meadows, S. W. Fesik, NMR structure and mutagenesis of the Fas (APO-1/CD95) death domain. Nature 384, 638–641 (1996).
77
E. Liepinsh, L. L. Ilag, G. Otting, C. F. Ibañez, NMR structure of the death domain of the p75 neurotrophin receptor. EMBO J. 16, 4999–5005 (1997).
78
S. F. Sukits, L.-L. Lin, S. Hsu, K. Malakian, R. Powers, G.-Y. Xu, Solution structure of the tumor necrosis factor receptor-1 death domain. J. Mol. Biol. 310, 895–906 (2001).
79
E.-J. Jeong, S. Bang, T. H. Lee, Y. I. Park, W.-S. Sim, K.-S. Kim, The solution structure of FADD death domain. Structural basis of death domain interactions of Fas and FADD. J. Biol. Chem. 274, 16337–16342 (1999).
80
H. Berglund, D. Olerenshaw, A. Sankar, M. Federwisch, N. Q. McDonald, P. C. Driscoll, The three-dimensional solution structure and dynamic properties of the human FADD death domain. J. Mol. Biol. 302, 171–188 (2000).
81
J. Silke, R. Brink, Regulation of TNFRSF and innate immune signalling complexes by TRAFs and cIAPs. Cell Death Differ. 17, 35–45 (2010).
82
P Xie, TRAF molecules in cell signaling and in human diseases. J. Mol. Signal. 8, 7 (2013).
83
A. Ceccarelli, A. Di Venere, E. Nicolai, A. De Luca, V. Minicozzi, N. Rosato, A. M. Caccuri, G. Mei, TNFR-associated factor-2 (TRAF2): Not only a trimer. Biochemistry 54, 6153–6161 (2015).
84
Q. Yin, S. C. Lin, B. Lamothe, M. Lu, Y. C. Lo, G. Hura, L. Zheng, R. L. Rich, A. D. Campos, D. G. Myszka, M. J. Lenardo, B. G. Darnay, H. Wu, E2 interaction and dimerization in the crystal structure of TRAF6. Nat. Struct. Mol. Biol. 16, 658–666 (2009).
85
Q. Yin, B. Lamothe, B. G. Darnay, H. Wu, Structural basis for the lack of E2 interaction in the RING domain of TRAF2. Biochemistry 48, 10558–10567 (2009).
86
J. Napetschnig, H. Wu, Molecular basis of NF-κB signaling. Annu. Rev. Biophys. 42, 443–468 (2013).
87
B. K. Ganser-Pornillos, V. Chandrasekaran, O. Pornillos, J. G. Sodroski, W. I. Sundquist, M. Yeager, Hexagonal assembly of a restricting TRIM5α protein. Proc. Natl. Acad. Sci. U.S.A. 108, 534–539 (2011).
88
D. C. Goldstone, P. A. Walker, L. J. Calder, P. J. Coombs, J. Kirkpatrick, N. J. Ball, L. Hilditch, M. W. Yap, P. B. Rosenthal, J. P. Stoye, I. A. Taylor, Structural studies of postentry restriction factors reveal antiparallel dimers that enable avid binding to the HIV-1 capsid lattice. Proc. Natl. Acad. Sci. U.S.A. 111, 9609–9614 (2014).
89
D. Esposito, M. G. Koliopoulos, K. Rittinger, Structural determinants of TRIM protein function. Biochem. Soc. Trans. 45, 183–191 (2017).
90
P. D. Mace, C. Smits, D. L. Vaux, J. Silke, C. L. Day, Asymmetric recruitment of cIAPs by TRAF2. J. Mol. Biol. 400, 8–15 (2010).
91
C. Zheng, V. Kabaleeswaran, Y. Wang, G. Cheng, H. Wu, Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: Affinity, specificity, and regulation. Mol. Cell 38, 101–113 (2010).
92
T. C. Hales, The honeycomb conjecture. Discrete Comput. Geom. 25, 1–22 (2001).
93
C. Richter, S. Messerschmidt, G. Holeiter, J. Tepperink, S. Osswald, A. Zappe, M. Branschädel, V. Boschert, D. A. Mann, P. Scheurich, A. Krippner-Heidenreich, The tumor necrosis factor receptor stalk regions define responsiveness to soluble versus membrane-bound ligand. Mol. Cell Biol. 32, 2515–2529 (2012).
94
Q. Fu, T.-M. Fu, A. C. Cruz, P. Sengupta, S. K. Thomas, S. Wang, R. M. Siegel, H. Wu, J. J. Chou, Structural basis and functional role of intramembrane trimerization of the Fas/CD95 death receptor. Mol. Cell 61, 602–613 (2016).
95
L. Ban, W. Kuhtreiber, J. Butterworth, Y. Okubo, E. S. Vanamee, D. L. Faustman, Strategic internal covalent cross-linking of TNF produces a stable TNF trimer with improved TNFR2 signaling. Mol. Cell. Ther. 3, 7 (2015).
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Published In
Science Signaling
Volume 11 | Issue 511
January 2018
January 2018
Copyright
Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
This is an article distributed under the terms of the Science Journals Default License.
Submission history
Received: 26 July 2017
Accepted: 16 November 2017
Acknowledgments
É.S.V. owns stocks in FusionBio Inc. D.L.F. declares that she has no competing interests.
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- Éva S. Vanamee,
- Denise L. Faustman
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