Structural Biology of Auxin Signal Transduction

  • Hongwei Jing
  • Lucia C. StraderEmail author


The phytohormone auxin is a central regulator of plant growth and development and is required for response to multiple environmental and developmental cues. Primary auxin response is mediated by several protein families, including members of the TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX PROTEIN (TIR1/AFB) family of F-box proteins, the AUXIN RESPONSE FACTOR (ARF) family of transcription factors, and the Auxin/INDOLE-3-ACETIC ACID (Aux/IAA) family of repressor proteins. Structures of multiple domains of each of these protein families have revealed molecular insight into auxin signal transduction. Here, we provide an overview of the structural details of auxin signaling revealed by these studies and explore questions and models suggested by these structural data.


  1. Abel S, Theologis A (1996) Early genes and auxin action. Plant Physiol 111:9–17CrossRefPubMedPubMedCentralGoogle Scholar
  2. Blakeslee JJ, Bandyopadhyay A, Lee OR, Mravec J, Titapiwatanakun B, Sauer M, Makam SN, Cheng Y, Bouchard R, Adamec J et al (2007) Interactions among PIN-FORMED and P-glycoprotein auxin transporters in Arabidopsis. Plant Cell 19:131–147CrossRefPubMedPubMedCentralGoogle Scholar
  3. Boer DR, Freire-Rios A, van den Berg WAM, Saaki T, Manfield IW, Kepinski S, Lopez-Vidrieo I, Franco-Zorrilla JM, de Vries SC, Solano R et al (2014) Structural basis for DNA binding specificity by the auxin-dependent ARF transcription factors. Cell 156:577–589CrossRefPubMedGoogle Scholar
  4. Calderón Villalobos LIA, Lee S, De Oliveira C, Ivetac A, Brandt W, Armitage L, Sheard LB, Tan X, Parry G, Mao HB et al (2012) A combinatorial TIR1/AFB-Aux/IAA co-receptor system for differential sensing of auxin. Nat Chem Biol 8:477–485CrossRefPubMedGoogle Scholar
  5. Calderon-Villalobos LI, Tan X, Zheng N, Estelle M (2010) Auxin perception-structural insights. Cold Spring Harb Perspect Biol 2:a005546CrossRefPubMedPubMedCentralGoogle Scholar
  6. Causier B, Lloyd J, Stevens L, Davies B (2012) TOPLESS co-repressor interactions and their evolutionary conservation in plants. Plant Signal Behav 7:325–328CrossRefPubMedPubMedCentralGoogle Scholar
  7. Chandler JW (2016) Auxin response factors. Plant Cell Environ 39:1014–1028CrossRefPubMedGoogle Scholar
  8. Colson K, Doss DS, Swift R, Tariman J, Thomas TE (2004) Bortezomib, a newly approved proteasome inhibitor for the treatment of multiple myeloma: nursing implications. Clin J Oncol Nurs 8:473–480CrossRefPubMedGoogle Scholar
  9. Dezfulian MH, Jalili E, Roberto DK, Moss BL, Khoo K, Nemhauser JL, Crosby WL (2016) Oligomerization of SCFTIR1 is essential for Aux/IAA degradation and auxin signaling in Arabidopsis. PLoS Genet 12:e1006301CrossRefPubMedPubMedCentralGoogle Scholar
  10. Dharmasiri N, Dharmasiri S, Estelle M (2005a) The F-box protein TIR1 is an auxin receptor. Nature 435:441–445CrossRefPubMedGoogle Scholar
  11. Dharmasiri N, Dharmasiri S, Weijers D, Lechner E, Yamada M, Hobbie L, Ehrismann JS, Jürgens G, Estelle M (2005b) Plant development is regulated by a family of auxin receptor F box proteins. Dev Cell 9:109–119CrossRefPubMedGoogle Scholar
  12. Dinesh DC, Kovermann M, Gopalswamy M, Hellmuth A, Calderon Villalobos LI, Lilie H, Balbach J, Abel S (2015) Solution structure of the PsIAA4 oligomerization domain reveals interaction modes for transcription factors in early auxin response. Proc Natl Acad Sci U S A 112:6230–6235CrossRefPubMedPubMedCentralGoogle Scholar
  13. Enders TA, Strader LC (2015) Auxin activity: past, present, and future. Am J Bot 102:180–196CrossRefPubMedPubMedCentralGoogle Scholar
  14. Fukaki H, Tameda S, Masuda H, Tasaka M (2002) Lateral root formation is blocked by a gain-of-function mutation in the SOLITARY-ROOT/IAA14 gene of Arabidopsis. Plant J 29:153–168CrossRefPubMedGoogle Scholar
  15. Gagne JM, Downes BP, Shiu SH, Durski AM, Vierstra RD (2002) The F-box subunit of the SCF E3 complex is encoded by a diverse superfamily of genes in Arabidopsis. Proc Natl Acad Sci U S A 99:11519–11524CrossRefPubMedPubMedCentralGoogle Scholar
  16. Gray WM, Kepinski S, Rouse D, Leyser O, Estelle M (2001) Auxin regulates SCFTIR1-dependent degradation of AUX/IAA proteins. Nature 414:271–276CrossRefPubMedGoogle Scholar
  17. Guilfoyle TJ, Hagen G (2001) Auxin response factors. J Plant Growth Regul 20:281–291CrossRefGoogle Scholar
  18. Guilfoyle TJ, Hagen G (2007) Auxin response factors. Curr Opin Plant Biol 10:453–460CrossRefPubMedGoogle Scholar
  19. Guilfoyle TJ, Hagen G (2012) Getting a grasp on domain III/IV responsible for auxin response factor-IAA protein interactions. Plant Sci 190:82–88CrossRefPubMedGoogle Scholar
  20. Hamann T, Mayer U, Jürgens G (1999) The auxin-insensitive bodenlos mutation affects primary root formation and apical-basal patterning in the Arabidopsis embryo. Development 126:1387–1395PubMedGoogle Scholar
  21. Hamann T, Benkova E, Bäurle I, Kientz M, Jürgens G (2002) The Arabidopsis BODENLOS gene encodes an auxin response protein inhibiting MONOPTEROS-mediated embryo patterning. Genes Dev 16:1610–1615CrossRefPubMedPubMedCentralGoogle Scholar
  22. Han M, Park Y, Kim I, Kim EH, Yu TK, Rhee S, Suh JY (2014) Structural basis for the auxin-induced transcriptional regulation by Aux/IAA17. Proc Natl Acad Sci U S A 111:18613–18618CrossRefPubMedPubMedCentralGoogle Scholar
  23. Havens KA, Guseman JM, Jang SS, Pierre-Jerome E, Bolten N, Klavins E, Nemhauser JL (2012) A synthetic approach reveals extensive tunability of auxin signaling. Plant Physiol 160:135–142CrossRefPubMedPubMedCentralGoogle Scholar
  24. Hussain M, Lu Y, Liu YQ, Su K, Zhang J, Liu J, Zhou GB (2016) Skp1: implications in cancer and SCF-oriented anti-cancer drug discovery. Pharmacol Res 111:34–42CrossRefPubMedGoogle Scholar
  25. Jing H, Yang X, Zhang J, Liu X, Zheng H, Dong G, Nian J, Feng J, Xia B, Qian Q et al (2015) Peptidyl-prolyl isomerization targets rice Aux/IAAs for proteasomal degradation during auxin signalling. Nat Commun 6:7395CrossRefPubMedGoogle Scholar
  26. Kagale S, Rozwadowski K (2011) EAR motif-mediated transcriptional repression in plants an underlying mechanism for epigenetic regulation of gene expression. Epigenetics-Us 6:141–146CrossRefGoogle Scholar
  27. Kagale S, Links MG, Rozwadowski K (2010) Genome-wide analysis of ethylene-responsive element binding factor-associated amphiphilic repression motif-containing transcriptional regulators in Arabidopsis. Plant Physiol 152:1109–1134CrossRefPubMedPubMedCentralGoogle Scholar
  28. Ke J, Ma H, Gu X, Thelen A, Brunzelle JS, Li J, Xu HE, Melcher K (2015) Structural basis for recognition of diverse transcriptional repressors by the TOPLESS family of corepressors. Sci Adv 1:e1500107CrossRefPubMedPubMedCentralGoogle Scholar
  29. Kepinski S, Leyser O (2004) Auxin-induced SCFTIR1-Aux/IAA interaction involves stable modification of the SCFTIR1 complex. Proc Natl Acad Sci U S A 101:12381–12386CrossRefPubMedPubMedCentralGoogle Scholar
  30. Kepinski S, Leyser O (2005) The Arabidopsis F-box protein TIR1 is an auxin receptor. Nature 435:446–451CrossRefPubMedGoogle Scholar
  31. Kim BC, Soh MS, Kang BJ, Furuya M, Nam HG (1996) Two dominant photomorphogenic mutations of Arabidopsis thaliana identified as suppressor mutations of hy2. Plant J 9:441–456CrossRefPubMedGoogle Scholar
  32. Kim J, Harter K, Theologis A (1997) Protein-protein interactions among the Aux/IAA proteins. Proc Natl Acad Sci U S A 94:11786–11791CrossRefPubMedPubMedCentralGoogle Scholar
  33. Korasick DA, Westfall CS, Lee SG, Nanao MH, Dumas R, Hagen G, Guilfoyle TJ, Jez JM, Strader LC (2014) Molecular basis for AUXIN RESPONSE FACTOR protein interaction and the control of auxin response repression. Proc Natl Acad Sci U S A 111:5427–5432CrossRefPubMedPubMedCentralGoogle Scholar
  34. Lee S, Sundaram S, Armitage L, Evans JP, Hawkes T, Kepinski S, Ferro N, Napier RM (2014) Defining binding efficiency and specificity of auxins for SCFTIR1/AFB-Aux/IAA co-receptor complex formation. ACS Chem Biol 9:673–682CrossRefPubMedGoogle Scholar
  35. Leyser O (2006) Dynamic integration of auxin transport and signalling. Curr Biol 16:R424–R433CrossRefPubMedGoogle Scholar
  36. Leyser HMO, Pickett FB, Dharmasiri S, Estelle M (1996) Mutations in the AXR3 gene of Arabidopsis result in altered auxin response including ectopic expression from the SAUR-AC1 promoter. Plant J 10:403–413CrossRefPubMedGoogle Scholar
  37. Li SB, Xie ZZ, Hu CG, Zhang JZ (2016) A review of auxin response factors (ARFs) in plants. Front Plant Sci 7:47PubMedPubMedCentralGoogle Scholar
  38. Liscum E, Reed JW (2002) Genetics of Aux/IAA and ARF action in plant growth and development. Plant Mol Biol 49:387–400CrossRefPubMedGoogle Scholar
  39. Long JA, Ohno C, Smith ZR, Meyerowitz EM (2006) TOPLESS regulates apical embryonic fate in Arabidopsis. Science 312:1520–1523CrossRefGoogle Scholar
  40. Luo Z, Pan Y, Jeong LS, Liu J, Jia L (2012) Inactivation of the Cullin (CUL)-RING E3 ligase by the NEDD8-activating enzyme inhibitor MLN4924 triggers protective autophagy in cancer cells. Autophagy 8:1677–1679CrossRefPubMedPubMedCentralGoogle Scholar
  41. Mockaitis K, Estelle M (2008) Auxin receptors and plant development: a new signaling paradigm. Annu Rev Cell Dev Biol 24:55–80CrossRefPubMedGoogle Scholar
  42. Nagpal P, Walker LM, Young JC, Sonawala A, Timpte C, Estelle M, Reed JW (2000) AXR2 encodes a member of the Aux/IAA protein family. Plant Physiol 123:563–573CrossRefPubMedPubMedCentralGoogle Scholar
  43. Nanao MH, Vinos-Poyo T, Brunoud G, Thevenon E, Mazzoleni M, Mast D, Laine S, Wang SC, Hagen G, Li HB et al (2014) Structural basis for oligomerization of auxin transcriptional regulators. Nat Commun 5:3617CrossRefPubMedGoogle Scholar
  44. Noda Y, Kohjima M, Izaki T, Ota K, Yoshinaga S, Inagaki F, Ito T, Sumimoto H (2003) Molecular recognition in dimerization between PB1 domains. J Biol Chem 278:43516–43524CrossRefPubMedGoogle Scholar
  45. Orlowski RZ, Kuhn DJ (2008) Proteasome inhibitors in cancer therapy: lessons from the first decade. Clin Cancer Res 14:1649–1657CrossRefPubMedGoogle Scholar
  46. Overvoorde PJ, Okushima Y, Alonso JM, Chan A, Chang C, Ecker JR, Hughes B, Liu A, Onodera C, Quach H et al (2005) Functional genomic analysis of the AUXIN/INDOLE-3-ACETIC ACID gene family members in Arabidopsis thaliana. Plant Cell 17:3282–3300CrossRefPubMedPubMedCentralGoogle Scholar
  47. Parry G, Calderon-Villalobos LI, Prigge M, Peret B, Dharmasiri S, Itoh H, Lechner E, Gray WM, Bennett M, Estelle M (2009) Complex regulation of the TIR1/AFB family of auxin receptors. Proc Natl Acad Sci U S A 106:22540–22545CrossRefPubMedPubMedCentralGoogle Scholar
  48. Petzold G, Fischer ES, Thoma NH (2016) Structural basis of lenalidomide-induced CK1 alpha degradation by the CRL4(CRBN) ubiquitin ligase. Nature 532:127–130CrossRefPubMedGoogle Scholar
  49. Pickart CM (2001) Mechanisms underlying ubiquitination. Annu Rev Biochem 70:503–533CrossRefPubMedGoogle Scholar
  50. Pierre-Jerome E, Moss BL, Lanctot A, Hagemena A, Nemhauser JL (2016) Functional analysis of molecular interactions in synthetic auxin response circuits. Proc Natl Acad Sci 113:11354–11359CrossRefPubMedGoogle Scholar
  51. Reed JW (2001) Roles and activities of Aux/IAA proteins in Arabidopsis. Trends Plant Sci 6:420–425CrossRefPubMedGoogle Scholar
  52. Remington DL, Vision TJ, Guilfoyle TJ, Reed JW (2004) Contrasting modes of diversification in the Aux/IAA and ARF gene families. Plant Physiol 135:1738–1752CrossRefPubMedPubMedCentralGoogle Scholar
  53. Rinaldi MA, Liu J, Enders TA, Bartel B, Strader LC (2012) A gain-of-function mutation in IAA16 confers reduced responses to auxin and abscisic acid and impedes plant growth and fertility. Plant Mol Biol 79:359–373CrossRefPubMedPubMedCentralGoogle Scholar
  54. Rogg LE, Lasswell J, Bartel B (2001) A gain-of-function mutation in IAA28 suppresses lateral root development. Plant Cell 13:465–480CrossRefPubMedPubMedCentralGoogle Scholar
  55. Rouse D, Mackay P, Stirnberg P, Estelle M, Leyser O (1998) Changes in auxin response from mutations in an AUX/IAA gene. Science 279:1371–1373CrossRefPubMedGoogle Scholar
  56. Ruegger M, Dewey E, Hobbie L, Brown D, Bernasconi P, Turner J, Muday G, Estelle M (1997) Reduced naphthylphthalamic acid binding in the tir3 mutant of Arabidopsis is associated with a reduction in polar auxin transport and diverse morphological defects. Plant Cell 9:745–757CrossRefPubMedPubMedCentralGoogle Scholar
  57. Ruegger M, Dewey E, Gray WM, Hobbie L, Turner J, Estelle M (1998) The TIR1 protein of Arabidopsis functions in auxin response and is related to human SKP2 and yeast Grr1p. Genes Dev 12:198–207CrossRefPubMedPubMedCentralGoogle Scholar
  58. Salehin M, Bagchi R, Estelle M (2015) SCFTIR1/AFB-based auxin perception: mechanism and role in plant growth and development. Plant Cell 27:9–19CrossRefPubMedPubMedCentralGoogle Scholar
  59. Sauer M, Robert S, Kleine-Vehn J (2013) Auxin: simply complicated. J Exp Bot 64:2565–2577CrossRefPubMedGoogle Scholar
  60. Shimizu-Mitao Y, Kakimoto T (2014) Auxin sensitivities of all Arabidopsis Aux/IAAs for degradation in the presence of every TIR1/AFB. Plant Cell Physiol 55:1450–1459CrossRefPubMedGoogle Scholar
  61. Soucy TA, Smith PG, Milhollen MA, Berger AJ, Gavin JM, Adhikari S, Brownell JE, Burke KE, Cardin DP, Critchley S et al (2009) An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458:732–736CrossRefPubMedGoogle Scholar
  62. Su SH, Gray WM, Masson PH (2015) Auxin: shape matters. Nat Plants 1:15097CrossRefPubMedGoogle Scholar
  63. Sumimoto H, Kamakura S, Ito T (2007) Structure and function of the PB1 domain, a protein interaction module conserved in animals, fungi, amoebas, and plants. Sci STKE 2007:re6CrossRefPubMedGoogle Scholar
  64. Szemenyei H, Hannon M, Long JA (2008) TOPLESS mediates auxin-dependent transcriptional repression during Arabidopsis embryogenesis. Science 319:1384–1386CrossRefGoogle Scholar
  65. Tan X, Calderon-Villalobos LIA, Sharon M, Zheng C, Robinson CV, Estelle M, Zheng N (2007) Mechanism of auxin perception by the TIR1 ubiquitin ligase. Nature 446:640–645CrossRefPubMedGoogle Scholar
  66. Tatematsu K, Kumagai S, Muto H, Sato A, Watahiki MK, Harper RM, Liscum E, Yamamoto KT (2004) MASSUGU2 encodes Aux/IAA19, an auxin-regulated protein that functions together with the transcriptional activator NPH4/ARF7 to regulate differential growth responses of hypocotyl and formation of lateral roots in Arabidopsis thaliana. Plant Cell 16:379–393CrossRefPubMedPubMedCentralGoogle Scholar
  67. Terrile MC, Paris R, Calderon-Villalobos LIA, Iglesias MJ, Lamattina L, Estelle M, Casalongue CA (2012) Nitric oxide influences auxin signaling through S-nitrosylation of the Arabidopsis TRANSPORT INHIBITOR RESPONSE 1 auxin receptor. Plant J 70:492–500CrossRefPubMedPubMedCentralGoogle Scholar
  68. Theologis A, Huynh TV, Davis RW (1985) Rapid induction of specific mRNAs by auxin in pea epicotyl tissue. J Mol Biol 183:53–68CrossRefPubMedGoogle Scholar
  69. Tian Q, Reed JW (1999) Control of auxin-regulated root development by the Arabidopsis thaliana SHY2/IAA3 gene. Development 126:711–721PubMedGoogle Scholar
  70. Tiwari SB, Wang X-J, Hagen G, Guilfoyle TJ (2001) Aux/IAA proteins are active repressors, and their stability and activity are modulated by auxin. Plant Cell 13:2809–2822CrossRefPubMedPubMedCentralGoogle Scholar
  71. Tiwari SB, Hagen G, Guilfoyle T (2003) The roles of auxin response factor domains in auxin-responsive transcription. Plant Cell 15:533–543CrossRefPubMedPubMedCentralGoogle Scholar
  72. Uehara T, Okushima Y, Mimura T, Tasaka M, Fukaki H (2008) Domain II mutations in CRANE/IAA18 suppress lateral root formation and affect shoot development in Arabidopsis thaliana. Plant Cell Physiol 49:1025–1038CrossRefPubMedGoogle Scholar
  73. Ulmasov T, Hagen G, Guilfoyle TJ (1997a) ARF1, a transcription factor that binds to auxin response elements. Science 276:1865–1868CrossRefPubMedGoogle Scholar
  74. Ulmasov T, Murfett J, Hagen G, Guilfoyle TJ (1997b) Aux/IAA proteins repress expression of reporter genes containing natural and highly active synthetic auxin response elements. Plant Cell 9:1963–1971CrossRefPubMedPubMedCentralGoogle Scholar
  75. Ulmasov T, Hagen G, Guilfoyle TJ (1999a) Activation and repression of transcription by auxin-response factors. Proc Natl Acad Sci U S A 96:5844–5849CrossRefPubMedPubMedCentralGoogle Scholar
  76. Ulmasov T, Hagen G, Guilfoyle TJ (1999b) Dimerization and DNA binding of auxin response factors. Plant J 19:309–319CrossRefPubMedGoogle Scholar
  77. Walker JC, Key JL (1982) Isolation of cloned cDNAs to auxin-responsive poly(A)RNAs of elongating soybean hypocotyl. Proc Natl Acad Sci U S A 79:7185–7189CrossRefPubMedPubMedCentralGoogle Scholar
  78. Wang RH, Zhang Y, Kieffer M, Yu H, Kepinski S, Estelle M (2016) HSP90 regulates temperature-dependent seedling growth in Arabidopsis by stabilizing the auxin co-receptor F-box protein TIR1. Nat Commun 7:10269CrossRefPubMedPubMedCentralGoogle Scholar
  79. Wilson AK, Pickett FB, Turner JC, Estelle M (1990) A dominant mutation in Arabidopsis confers resistance to auxin, ethylene and abscisic acid. Mol Gen Genet 222:377–383CrossRefPubMedGoogle Scholar
  80. Wu S, Yu L (2016) Targeting cullin-RING ligases for cancer treatment: rationales, advances and therapeutic implications. Cytotechnology 68:1–8CrossRefPubMedGoogle Scholar
  81. Yang XQ, Lee S, So JH, Dharmasiri S, Dharmasiri N, Ge L, Jensen C, Hangarter R, Hobbie L, Estelle M (2004) The IAA1 protein is encoded by AXR5 and is a substrate of SCFTIR1. Plant J 40:772–782CrossRefPubMedGoogle Scholar
  82. Zenser N, Ellsmore A, Leasure C, Callis J (2001) Auxin modulates the degradation rate of Aux/IAA proteins. Proc Natl Acad Sci U S A 98:11795–11800CrossRefPubMedPubMedCentralGoogle Scholar
  83. Zhao Y, Morgan MA, Sun Y (2014) Targeting Neddylation pathways to inactivate Cullin-RING ligases for anticancer therapy. Antioxid Redox Signal 21:2383–2400CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of BiologyWashington University in St. LouisSt. LouisUSA

Personalised recommendations