9lgs | pdb_00009lgs

R-degron fused ZZ-domain of the Arabidopsis thaliana E3 ubiquitin-protein ligase BIG

Structural highlights

9lgs is a 3 chain structure with sequence from Arabidopsis thaliana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.5Å
Ligands:	NI, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BIG_ARATH Required for auxin efflux and polar auxin transport (PAT) influencing auxin-mediated developmental responses (e.g. cell elongation, apical dominance, lateral root production, inflorescence architecture, general growth and development). Controls the elongation of the pedicels and stem internodes through auxin action. Involved in the expression modulation of light-regulated genes. Represses CAB1 and CAB3 genes expression in etiolated seedlings. Confers sensitivity to the auxin transport inhibitors N-1-naphthylphthalamic acid (NPA), 2-carboxyphenyl-3-phenylpropane-l,2-dione (CPD), and methyl-2-chloro-9-hydroxyfluorene-9-carboxylate (CFM). Influences the polarized subcellular distribution of the auxin transporter PIN1 in response to auxin transport inhibitors. Plays a role in the regulation of responses to phytohormones such as auxin, cytokinins, ethylene and gibberellic acid (GA), particularly during light-mediated stimuli (e.g. shade ovoidance, etiolation). Required for pericycle cell activation to form lateral root primordia (LRP) in both high and low phosphate P conditions. Necessary for the plant-growth promotion and lateral root development mediated by the fungus Trichoderma virens.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

Publication Abstract from PubMed

Eukaryotic cells have evolved sophisticated quality control mechanisms to eliminate aggregation-prone proteins that compromise cellular health. Central to this defense is the ubiquitin-proteasome system, where UBR4 acts as an essential E4 ubiquitin ligase, amplifying degradation marks on defective proteins. Cryo-electron microscopy analysis of UBR4 in complex with its cofactors KCMF1 and CALM1 reveals a massive 1.3-megadalton ring structure, featuring a central substrate-binding arena and flexibly attached catalytic units. Our structure shows how UBR4 binds substrate and extends lysine-48-specific ubiquitin chains. Efficient substrate targeting depends on both preubiquitination and specific N-degrons, with KCMF1 acting as a key substrate filter. The architecture of the E4 megacomplex is conserved across eukaryotes, but species-specific adaptations allow UBR4 to perform its precisely tuned quality control function in diverse cellular environments.

Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.,Grabarczyk DB, Ehrmann JF, Murphy P, Yang WS, Kurzbauer R, Bell LE, Deszcz L, Neuhold J, Schleiffer A, Shulkina A, Lee J, Shin JS, Meinhart A, Versteeg GA, Zavodszky E, Song HK, Hegde RS, Clausen T Science. 2025 Aug 28;389(6763):909-914. doi: 10.1126/science.adv9309. Epub 2025 , Aug 28. PMID:40875847^[10]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gil P, Dewey E, Friml J, Zhao Y, Snowden KC, Putterill J, Palme K, Estelle M, Chory J. BIG: a calossin-like protein required for polar auxin transport in Arabidopsis. Genes Dev. 2001 Aug 1;15(15):1985-97. PMID:11485992 doi:10.1101/gad.905201
↑ Kanyuka K, Praekelt U, Franklin KA, Billingham OE, Hooley R, Whitelam GC, Halliday KJ. Mutations in the huge Arabidopsis gene BIG affect a range of hormone and light responses. Plant J. 2003 Jul;35(1):57-70. PMID:12834402 doi:10.1046/j.1365-313x.2003.01779.x
↑ Desgagné-Penix I, Eakanunkul S, Coles JP, Phillips AL, Hedden P, Sponsel VM. The auxin transport inhibitor response 3 (tir3) allele of BIG and auxin transport inhibitors affect the gibberellin status of Arabidopsis. Plant J. 2005 Jan;41(2):231-42. PMID:15634200 doi:10.1111/j.1365-313X.2004.02287.x
↑ López-Bucio J, Hernández-Abreu E, Sánchez-Calderón L, Pérez-Torres A, Rampey RA, Bartel B, Herrera-Estrella L. An auxin transport independent pathway is involved in phosphate stress-induced root architectural alterations in Arabidopsis. Identification of BIG as a mediator of auxin in pericycle cell activation. Plant Physiol. 2005 Feb;137(2):681-91. PMID:15681664 doi:10.1104/pp.104.049577
↑ Yamaguchi N, Suzuki M, Fukaki H, Morita-Terao M, Tasaka M, Komeda Y. CRM1/BIG-mediated auxin action regulates Arabidopsis inflorescence development. Plant Cell Physiol. 2007 Sep;48(9):1275-90. PMID:17652113 doi:10.1093/pcp/pcm094
↑ Contreras-Cornejo HA, Macías-Rodríguez L, Cortés-Penagos C, López-Bucio J. Trichoderma virens, a plant beneficial fungus, enhances biomass production and promotes lateral root growth through an auxin-dependent mechanism in Arabidopsis. Plant Physiol. 2009 Mar;149(3):1579-92. PMID:19176721 doi:10.1104/pp.108.130369
↑ Li HM, Altschmied L, Chory J. Arabidopsis mutants define downstream branches in the phototransduction pathway. Genes Dev. 1994 Feb 1;8(3):339-49. PMID:8314087 doi:10.1101/gad.8.3.339
↑ Ruegger M, Dewey E, Hobbie L, Brown D, Bernasconi P, Turner J, Muday G, Estelle M. 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. 1997 May;9(5):745-57. PMID:9165751 doi:10.1105/tpc.9.5.745
↑ Sponsel VM, Schmidt FW, Porter SG, Nakayama M, Kohlstruk S, Estelle M. Characterization of new gibberellin-responsive semidwarf mutants of arabidopsis. Plant Physiol. 1997 Nov;115(3):1009-20. PMID:9390435 doi:10.1104/pp.115.3.1009
↑ Grabarczyk DB, Ehrmann JF, Murphy P, Yang WS, Kurzbauer R, Bell LE, Deszcz L, Neuhold J, Schleiffer A, Shulkina A, Lee J, Shin JS, Meinhart A, Versteeg GA, Zavodszky E, Song HK, Hegde RS, Clausen T. Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control. Science. 2025 Aug 28;389(6763):909-914. PMID:40875847 doi:10.1126/science.adv9309

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OCA

[1] Gil P, Dewey E, Friml J, Zhao Y, Snowden KC, Putterill J, Palme K, Estelle M, Chory J. BIG: a calossin-like protein required for polar auxin transport in Arabidopsis. Genes Dev. 2001 Aug 1;15(15):1985-97. PMID:11485992 doi:10.1101/gad.905201

[2] Kanyuka K, Praekelt U, Franklin KA, Billingham OE, Hooley R, Whitelam GC, Halliday KJ. Mutations in the huge Arabidopsis gene BIG affect a range of hormone and light responses. Plant J. 2003 Jul;35(1):57-70. PMID:12834402 doi:10.1046/j.1365-313x.2003.01779.x

[3] Desgagné-Penix I, Eakanunkul S, Coles JP, Phillips AL, Hedden P, Sponsel VM. The auxin transport inhibitor response 3 (tir3) allele of BIG and auxin transport inhibitors affect the gibberellin status of Arabidopsis. Plant J. 2005 Jan;41(2):231-42. PMID:15634200 doi:10.1111/j.1365-313X.2004.02287.x

[4] López-Bucio J, Hernández-Abreu E, Sánchez-Calderón L, Pérez-Torres A, Rampey RA, Bartel B, Herrera-Estrella L. An auxin transport independent pathway is involved in phosphate stress-induced root architectural alterations in Arabidopsis. Identification of BIG as a mediator of auxin in pericycle cell activation. Plant Physiol. 2005 Feb;137(2):681-91. PMID:15681664 doi:10.1104/pp.104.049577

[5] Yamaguchi N, Suzuki M, Fukaki H, Morita-Terao M, Tasaka M, Komeda Y. CRM1/BIG-mediated auxin action regulates Arabidopsis inflorescence development. Plant Cell Physiol. 2007 Sep;48(9):1275-90. PMID:17652113 doi:10.1093/pcp/pcm094

[6] Contreras-Cornejo HA, Macías-Rodríguez L, Cortés-Penagos C, López-Bucio J. Trichoderma virens, a plant beneficial fungus, enhances biomass production and promotes lateral root growth through an auxin-dependent mechanism in Arabidopsis. Plant Physiol. 2009 Mar;149(3):1579-92. PMID:19176721 doi:10.1104/pp.108.130369

[7] Li HM, Altschmied L, Chory J. Arabidopsis mutants define downstream branches in the phototransduction pathway. Genes Dev. 1994 Feb 1;8(3):339-49. PMID:8314087 doi:10.1101/gad.8.3.339

[8] Ruegger M, Dewey E, Hobbie L, Brown D, Bernasconi P, Turner J, Muday G, Estelle M. 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. 1997 May;9(5):745-57. PMID:9165751 doi:10.1105/tpc.9.5.745

[9] Sponsel VM, Schmidt FW, Porter SG, Nakayama M, Kohlstruk S, Estelle M. Characterization of new gibberellin-responsive semidwarf mutants of arabidopsis. Plant Physiol. 1997 Nov;115(3):1009-20. PMID:9390435 doi:10.1104/pp.115.3.1009

[10] Grabarczyk DB, Ehrmann JF, Murphy P, Yang WS, Kurzbauer R, Bell LE, Deszcz L, Neuhold J, Schleiffer A, Shulkina A, Lee J, Shin JS, Meinhart A, Versteeg GA, Zavodszky E, Song HK, Hegde RS, Clausen T. Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control. Science. 2025 Aug 28;389(6763):909-914. PMID:40875847 doi:10.1126/science.adv9309

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9lgs | pdb_00009lgs

R-degron fused ZZ-domain of the Arabidopsis thaliana E3 ubiquitin-protein ligase BIG

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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