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- PDB-7xyz: TRIM E3 ubiquitin ligase -

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Basic information

Entry
Database: PDB / ID: 7xyz
TitleTRIM E3 ubiquitin ligase
ComponentsTripartite motif-containing protein 72
KeywordsMEMBRANE PROTEIN / TRIM / Tripartite motif / Ubiquitin ligase / Coiled coil / B-box / PRY-SPRY / LIGASE / METAL BINDING PROTEIN / TRIM72 / MG53
Function / homology
Function and homology information


muscle system process / negative regulation of insulin-like growth factor receptor signaling pathway / negative regulation of myotube differentiation / plasma membrane repair / vesicle budding from membrane / ubiquitin conjugating enzyme binding / mitogen-activated protein kinase kinase kinase binding / muscle organ development / phosphatidylserine binding / exocytosis ...muscle system process / negative regulation of insulin-like growth factor receptor signaling pathway / negative regulation of myotube differentiation / plasma membrane repair / vesicle budding from membrane / ubiquitin conjugating enzyme binding / mitogen-activated protein kinase kinase kinase binding / muscle organ development / phosphatidylserine binding / exocytosis / negative regulation of insulin receptor signaling pathway / cytoplasmic vesicle membrane / sarcolemma / protein homooligomerization / RING-type E3 ubiquitin transferase / ubiquitin protein ligase activity / proteasome-mediated ubiquitin-dependent protein catabolic process / zinc ion binding / identical protein binding
Similarity search - Function
Zinc finger, RING-type, eukaryotic / RING-type zinc-finger / : / SPRY-associated domain / SPRY-associated / PRY / Butyrophylin-like, SPRY domain / B-box zinc finger / B-Box-type zinc finger / B-box-type zinc finger ...Zinc finger, RING-type, eukaryotic / RING-type zinc-finger / : / SPRY-associated domain / SPRY-associated / PRY / Butyrophylin-like, SPRY domain / B-box zinc finger / B-Box-type zinc finger / B-box-type zinc finger / Zinc finger B-box type profile. / SPRY domain / B30.2/SPRY domain / B30.2/SPRY domain profile. / B30.2/SPRY domain superfamily / Domain in SPla and the RYanodine Receptor. / SPRY domain / Zinc finger, RING-type, conserved site / Zinc finger RING-type signature. / Ring finger / Zinc finger RING-type profile. / Zinc finger, RING-type / Concanavalin A-like lectin/glucanase domain superfamily / Zinc finger, RING/FYVE/PHD-type
Similarity search - Domain/homology
Tripartite motif-containing protein 72
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 4.62 Å
AuthorsPark, S.H. / Song, H.K.
Funding support Korea, Republic Of, 1items
OrganizationGrant numberCountry
Other government Korea, Republic Of
CitationJournal: Nat Struct Mol Biol / Year: 2023
Title: Structure and activation of the RING E3 ubiquitin ligase TRIM72 on the membrane.
Authors: Si Hoon Park / Juhyun Han / Byung-Cheon Jeong / Ju Han Song / Se Hwan Jang / Hyeongseop Jeong / Bong Heon Kim / Young-Gyu Ko / Zee-Yong Park / Kyung Eun Lee / Jaekyung Hyun / Hyun Kyu Song /
Abstract: Defects in plasma membrane repair can lead to muscle and heart diseases in humans. Tripartite motif-containing protein (TRIM)72 (mitsugumin 53; MG53) has been determined to rapidly nucleate vesicles ...Defects in plasma membrane repair can lead to muscle and heart diseases in humans. Tripartite motif-containing protein (TRIM)72 (mitsugumin 53; MG53) has been determined to rapidly nucleate vesicles at the site of membrane damage, but the underlying molecular mechanisms remain poorly understood. Here we present the structure of Mus musculus TRIM72, a complete model of a TRIM E3 ubiquitin ligase. We demonstrated that the interaction between TRIM72 and phosphatidylserine-enriched membranes is necessary for its oligomeric assembly and ubiquitination activity. Using cryogenic electron tomography and subtomogram averaging, we elucidated a higher-order model of TRIM72 assembly on the phospholipid bilayer. Combining structural and biochemical techniques, we developed a working molecular model of TRIM72, providing insights into the regulation of RING-type E3 ligases through the cooperation of multiple domains in higher-order assemblies. Our findings establish a fundamental basis for the study of TRIM E3 ligases and have therapeutic implications for diseases associated with membrane repair.
History
DepositionJun 2, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jul 12, 2023Provider: repository / Type: Initial release
Revision 1.1Aug 30, 2023Group: Data collection
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / diffrn_source / pdbx_validate_planes
Item: _diffrn_source.pdbx_synchrotron_site / _pdbx_validate_planes.type
Revision 1.2Oct 4, 2023Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.title / _citation.year
Revision 1.3Oct 11, 2023Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation.title ..._citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.4Nov 22, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.5Nov 29, 2023Group: Refinement description / Category: pdbx_initial_refinement_model

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Tripartite motif-containing protein 72
B: Tripartite motif-containing protein 72
C: Tripartite motif-containing protein 72
D: Tripartite motif-containing protein 72
hetero molecules


Theoretical massNumber of molelcules
Total (without water)208,24820
Polymers207,2014
Non-polymers1,04716
Water00
1
A: Tripartite motif-containing protein 72
B: Tripartite motif-containing protein 72
hetero molecules


Theoretical massNumber of molelcules
Total (without water)104,12410
Polymers103,6012
Non-polymers5238
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
C: Tripartite motif-containing protein 72
D: Tripartite motif-containing protein 72
hetero molecules


Theoretical massNumber of molelcules
Total (without water)104,12410
Polymers103,6012
Non-polymers5238
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)174.375, 174.375, 224.941
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number144
Space group name H-MP31
Space group name HallP31
Symmetry operation#1: x,y,z
#2: -y,x-y,z+1/3
#3: -x+y,-x,z+2/3
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
d_1ens_1(chain "A" and (resid 14 or resid 24 through 32...
d_2ens_1(chain "B" and (resid 14 or resid 24 through 32...
d_3ens_1(chain "C" and (resid 14 or resid 24 through 32...
d_4ens_1(chain "D" and (resid 14 or resid 24 through 32...

NCS oper:
IDCodeMatrixVector
1given(0.506226651754, 0.862361960895, 0.00815018127341), (0.86237803493, -0.506259047426, 0.00242935581317), (0.00622108705058, 0.00579873265166, -0.999963835734)86.7115961432, -150.880005858, 44.4125971949
2given(-0.494928711089, -0.868930358042, -0.00236723741586), (-0.868931512754, 0.494931641777, -0.000834332433075), (0.0018965974805, 0.00164403211309, -0.999996850033)-0.743731314767, -0.359331953815, 5.97040664717
3given(-0.999930832178, -0.00112478814039, -0.0117075066296), (0.00120502271621, -0.999975822948, -0.00684846258277), (-0.0116995205071, -0.00686209670097, 0.999908012194)87.0540296634, -151.453886116, -37.9908167646
4given(0.40208494032, 0.912238178178, 0.078416879827), (0.907345761325, -0.408470832121, 0.0993742859701), (0.122684025746, 0.0311943196837, -0.991955414445)88.8065380896, -154.640201743, 40.9956620781
5given(-0.346884990979, -0.925190061134, -0.153929054479), (-0.917471218808, 0.368799170454, -0.149109806957), (0.194723819015, 0.0895015231812, -0.976766149934)-1.68444731833, 3.50493195691, 1.09322935757
6given(-0.981595517291, -0.123436733525, -0.145717580444), (0.129189883731, -0.991145614952, -0.0306650273742), (-0.140642150065, -0.0489258906832, 0.988850869872)88.3301986653, -155.311567173, -34.6753802159

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Components

#1: Protein
Tripartite motif-containing protein 72 / Mitsugumin-53 / Mg53


Mass: 51800.301 Da / Num. of mol.: 4 / Mutation: C55S, C144S, C241S, K279H, A283H
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Trim72, Mg53 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q1XH17
#2: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 16 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop
Details: 100 mM MES-NaOH pH 6.5, 200 mM MgCl2, 0.5% (w/v) polyvinylpyrrolidone K15, 30% (w/v) 5/4 PO/OH

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Photon Factory / Beamline: AR-NE3A / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Oct 19, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 4.6→50 Å / Num. obs: 40138 / % possible obs: 94.9 % / Redundancy: 4.4 % / Biso Wilson estimate: 171.99 Å2 / CC1/2: 0.992 / Net I/σ(I): 7.53
Reflection shellResolution: 4.6→4.68 Å / Num. unique obs: 1552 / CC1/2: 0.985

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Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 7DEW

7dew
PDB Unreleased entry


Resolution: 4.62→35.79 Å / SU ML: 1.259 / Cross valid method: FREE R-VALUE / σ(F): 1.96 / Phase error: 58.5475
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.3484 1806 4.85 %
Rwork0.3121 35447 -
obs0.314 37253 88.66 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 332.94 Å2
Refinement stepCycle: LAST / Resolution: 4.62→35.79 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14220 0 16 0 14236
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.004814518
X-RAY DIFFRACTIONf_angle_d1.028119671
X-RAY DIFFRACTIONf_chiral_restr0.04982191
X-RAY DIFFRACTIONf_plane_restr0.00742600
X-RAY DIFFRACTIONf_dihedral_angle_d7.26191973
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2AX-RAY DIFFRACTIONTorsion NCS1.65343765072
ens_1d_3AX-RAY DIFFRACTIONTorsion NCS1.82520364071
ens_1d_4AX-RAY DIFFRACTIONTorsion NCS1.56130069949
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
4.62-4.740.45911280.41822586X-RAY DIFFRACTION82.9
4.74-4.880.5872670.4291365X-RAY DIFFRACTION44.39
4.88-5.040.45031280.41012374X-RAY DIFFRACTION77.61
5.04-5.210.40731390.39482830X-RAY DIFFRACTION92.2
5.22-5.420.45271500.40362972X-RAY DIFFRACTION95.71
5.42-5.670.4721280.44722391X-RAY DIFFRACTION79.11
5.67-5.970.4921500.43572949X-RAY DIFFRACTION94.86
5.97-6.340.46591380.43342937X-RAY DIFFRACTION95.91
6.34-6.820.59391560.42933012X-RAY DIFFRACTION98.35
6.83-7.510.44321620.40962988X-RAY DIFFRACTION96.98
7.51-8.570.44751470.36163030X-RAY DIFFRACTION99
8.58-10.760.29041510.24163040X-RAY DIFFRACTION97.97
10.77-35.790.21871620.18932973X-RAY DIFFRACTION97.42
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
16.6524999692-6.79565990543-0.760582106466.47176320722.835721175463.423796686080.9500215624481.387627480371.49546266066-0.980492140882-1.78131667836-1.33508595402-0.7070405022151.96413804051-0.4044713497714.862922919050.04521558546742.128738226911.760994727271.56760158966-0.55727259574919.8183547353-80.5363922092-19.2545853218
22.035817094711.15064511617-0.2999842476742.629380627921.018022683590.7142015847130.06856543201480.3338666398480.9223452123720.1288148437180.1926909767572.55710003127-2.32983393217-1.318093895920.6907479197362.939582348440.580687233124-0.6826747835520.474048040879-0.5716097170871.21418749892-3.38166301114-88.0289494824-30.8398592188
31.08970564339-0.7540977172140.1546221460510.735026630573-0.006667715170450.170591927922-0.75453101362-1.22181553751-0.1488172811371.011543036681.140812324720.2553755999750.251700729695-0.3566387662060.464885237977-0.3861320628512.387152398230.250175846396-0.941648787064-1.039565020060.502779610448-7.54621378768-107.324904223-37.392500346
49.28154051663-5.09744192943.455307539274.565315455-0.3179343132262.71516532439-0.476299982057-2.00443899844-2.072937560391.526875303992.090598936571.221238570641.449919158840.801697220707-0.87236521523.560523324453.14698737171.628916053085.670333947020.8315128638334.0250725393524.6640750685-14.069181542725.5039347306
53.85430605281-4.907364033750.4944293083797.03756572095-3.550077264793.611818090250.08849562840261.08851146561-1.64057589639-0.1725415587940.3204207473710.07540559950360.3531838974320.2473055241021.326969595253.921722322051.30231529631-0.7331854079653.75184937081-1.36921566191-0.81475742973466.4202554804-69.055486618818.9448330142
60.5075522015080.671112553383-0.02545661551233.19705400642-2.450141341354.1911302359-0.2929628926191.32933416328-0.5325439373930.4002963451320.0627596671189-0.9236038687612.284337116131.066989210540.2710346180293.703193613010.7443432741410.1420120444222.117445559820.7863948149010.24635614660590.161821229-56.11566233841.98208615514
71.20889632206-0.308537011942-0.7968555926633.656831475742.148644504792.707540524320.3255992867120.06552325915680.1299065285490.7989413894511.33641249118-1.22520020601-0.5872379344771.622246709790.5195261350960.9205449070091.59868956781-0.6057560371513.636537847970.1548280064570.7797607571495.9385856469-43.86015590383.79425039901
85.54219491909-5.673325402925.830691063727.25316424042-7.503296221797.751031162340.1856761028313.16378042463-1.15096483302-2.37608573372-0.3728512927091.742051528621.744567186982.72524960890.4442301949584.017316866460.9284177567-0.5228120119295.74340760372-2.418096295435.096792001980.7430751154-114.32263323217.2805076275
90.219339356431-0.322503116375-0.4342094083770.43002638360.6221251620840.8596240514711.014037713021.76267013708-0.620386045628-1.37175678499-1.05241266825-0.1060644169750.519082126271-0.524725155385-0.3936654173078.314583518133.09762733024-0.06882218072974.28072663737-1.582497817243.6164566195496.5677896103-131.04026618519.1991148905
100.630021767541-1.62747943807-0.4818016467484.006958905722.511218798641.60296118866-0.07828755999720.3898193172170.2671336662271.36340438377-0.7082697008782.054329811691.083102680990.2786654563840.4547873955393.657102074210.9416721163382.81773119574.162355822580.0337888000594-1.1542759130859.7761011722-57.019118687225.252719773
114.326356377762.207736999080.2232449996791.146520697560.1012442097610.00652056945547-0.6417690359760.1239222911661.266345076460.5736452890790.5864522304140.173623858145-0.524045798097-1.449481187070.3834148238553.498557379312.32674660155-0.1713500273093.23272371710.2697663371211.3766301543468.5090999881-37.63475072719.474328735
127.174608646933.927279060244.010834108726.526268962153.875248701662.90342276678-0.724004386572-1.916916020620.2926844677631.43417802534-0.799048516674-0.576823186286-0.55084439837-0.4894409043411.063403439992.53638969518-0.475842548604-0.3158574415892.04474389662-0.5004288538480.54780654036492.0135102424-45.09203780755.8072472214
134.645223825760.852512377981-0.1598404443215.747207881661.773881195032.798562333091.606817944570.3502474308870.375350679793-0.53025428053-0.199765100352-0.3665426536530.2778617432860.342773002056-0.7490067440690.6689437123150.567475028460.216948670934-0.866651397709-0.1185660722250.77895404255396.2399716389-46.925306658441.387628543
140.8470549890731.434434194281.34540797971.992144340231.420574033422.194519998570.7026272082320.624563650787-1.5880473132-1.966600387030.0426004457301-4.846657443632.822284327270.1897006808820.1206403217055.7505581941-0.9137997769931.114748546252.024223505511.53859342745.391625827496.52935021891-37.2680035204-21.7202181978
150.212379930527-0.315767332269-0.6278405652474.201060036772.691644682252.517358161040.3597512377870.558047671499-0.225987165082-2.224094466441.09693331193-2.28203487655-1.31123574390.410277963414-0.8623374370166.363322058140.2010043482341.243920585081.312333646780.5510810418395.80177059418-10.8873688567-20.1303499963-18.7003269096
162.3484874433-0.910232747158-1.685209159392.06207360856-0.5338903523113.90412216015-0.157716970603-0.2596924840230.06256502330940.6897497935811.16638036614-0.564647631091-0.6473724783050.8770527351110.9848943075952.408562309550.509381240754-0.8385773201172.14245380108-0.190830730875-1.3840387126920.3965787826-84.0994286573-10.5651996473
17-0.0334743247720.391661415192-0.9649207471070.370325545097-0.875814349633.0869840799-0.373671618142-0.32078451297-0.59756088059-1.12136822384-1.05304656418-0.7825385592242.8474660523.62466309813-1.184686095931.018464919430.569243262153-0.08508571634861.0422740658-0.831807677280.056194782033228.160423709-119.253377111-12.5631436539
181.722067514020.9627930123570.2093851800661.79770325353-0.4419486524381.669997323621.48671035041-0.308249456766-0.8480682594030.4578260916010.5947083176431.48789702126-0.488288664288-0.03064650253960.907384171921-0.017819022809-1.687845727580.227202088779-0.7911572887260.8751372998810.926989064545-8.74084989822-104.8896652065.97236726927
192.240258255082.23610982842-1.739687330428.38732020246-1.376228950671.343313198792.978589167423.77643375027-0.0782349188229-0.0869246214019-1.889278189263.8153135782-0.1209482961381.08336353699-0.9841208884924.472608005711.33002132993-0.9353304782983.09718532603-0.9711810702573.8550550563661.7742898269-130.516058635-10.9447929323
200.2595529528480.325548974630.1477031749310.4176591188120.2077375253020.2335262698711.11489376372-0.0786449281797-2.579333742490.3087574801190.7540969508630.3581277991280.822289270375-0.153406475329-1.748051353574.909460487213.39753197175-1.481400231246.512840394830.06554399180914.1636581885863.1248523131-156.103907762-17.1641483419
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

IDRefine TLS-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11chain 'D' and (resid 122 through 253 )DD122 - 253108 - 239
22chain 'D' and (resid 254 through 317 )DD254 - 317240 - 303
33chain 'D' and (resid 318 through 470 )DD318 - 470304 - 456
44chain 'A' and (resid 7 through 118 )AA7 - 1181 - 104
55chain 'A' and (resid 119 through 253 )AA119 - 253105 - 239
66chain 'A' and (resid 254 through 350 )AA254 - 350240 - 333
77chain 'A' and (resid 351 through 470 )AA351 - 470334 - 453
88chain 'B' and (resid 7 through 64 )BB7 - 641 - 58
99chain 'B' and (resid 65 through 121 )BB65 - 12159 - 107
1010chain 'B' and (resid 122 through 253 )BB122 - 253108 - 239
1111chain 'B' and (resid 254 through 283 )BB254 - 283240 - 269
1212chain 'B' and (resid 284 through 337 )BB284 - 337270 - 323
1313chain 'B' and (resid 338 through 470 )BB338 - 470324 - 456
1414chain 'C' and (resid 7 through 65 )CC7 - 651 - 59
1515chain 'C' and (resid 66 through 121 )CC66 - 12160 - 107
1616chain 'C' and (resid 122 through 231 )CC122 - 231108 - 217
1717chain 'C' and (resid 232 through 302 )CC232 - 302218 - 284
1818chain 'C' and (resid 303 through 470 )CC303 - 470285 - 452
1919chain 'D' and (resid 7 through 87 )DD7 - 871 - 73
2020chain 'D' and (resid 88 through 121 )DD88 - 12174 - 107

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