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- PDB-8cn6: CD59 in complex with CP-06 peptide -

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Basic information

Entry
Database: PDB / ID: 8cn6
TitleCD59 in complex with CP-06 peptide
Components
  • CD59 glycoprotein
  • Cyclic peptide CP-06
KeywordsLIPID BINDING PROTEIN / Peptide bound Complex / Terminal Complement inhibitor
Function / homology
Function and homology information


negative regulation of activation of membrane attack complex / complement binding / regulation of complement-dependent cytotoxicity / regulation of complement activation / Cargo concentration in the ER / COPII-mediated vesicle transport / tertiary granule membrane / specific granule membrane / COPI-mediated anterograde transport / transport vesicle ...negative regulation of activation of membrane attack complex / complement binding / regulation of complement-dependent cytotoxicity / regulation of complement activation / Cargo concentration in the ER / COPII-mediated vesicle transport / tertiary granule membrane / specific granule membrane / COPI-mediated anterograde transport / transport vesicle / endoplasmic reticulum-Golgi intermediate compartment membrane / Regulation of Complement cascade / ER to Golgi transport vesicle membrane / blood coagulation / vesicle / cell surface receptor signaling pathway / external side of plasma membrane / Golgi membrane / focal adhesion / Neutrophil degranulation / endoplasmic reticulum membrane / cell surface / extracellular space / extracellular exosome / membrane / plasma membrane
Similarity search - Function
Snake toxin/toxin-like / CD59 antigen, conserved site / Ly-6 / u-PAR domain signature. / Ly-6 antigen / uPA receptor -like domain / Ly-6 antigen/uPA receptor-like / Snake toxin and toxin-like protein / Snake toxin-like superfamily
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.43 Å
AuthorsBickel, J. / Ahmed, A. / Morgan, M. / Horrell, S. / El Omari, K. / Couves, E.C. / Bubeck, D. / Tate, E.
Funding supportEuropean Union, United Kingdom, 3items
OrganizationGrant numberCountry
European Research Council (ERC)864751European Union
Cancer Research UKC24523/A26234 United Kingdom
Engineering and Physical Sciences Research CouncilEP/L015498/1 United Kingdom
CitationJournal: Angew.Chem.Int.Ed.Engl. / Year: 2025
Title: Macrocyclic Peptide Probes for Immunomodulatory Protein CD59: Potent Modulators of Bacterial Toxin Activity and Antibody-Dependent Cytotoxicity.
Authors: Bickel, J.K. / Ahmed, A.I.S. / Pidd, A.B. / Morgan, R.M. / McAllister, T.E. / Horrell, S. / Couves, E.C. / Nagaraj, H. / Bartlett, E.J. / El Omari, K. / Kawamura, A. / Bubeck, D. / Tate, E.W.
History
DepositionFeb 22, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 13, 2024Provider: repository / Type: Initial release
Revision 1.1May 28, 2025Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: CD59 glycoprotein
B: CD59 glycoprotein
C: CD59 glycoprotein
D: CD59 glycoprotein
E: CD59 glycoprotein
F: CD59 glycoprotein
J: Cyclic peptide CP-06
G: Cyclic peptide CP-06
H: Cyclic peptide CP-06
hetero molecules


Theoretical massNumber of molelcules
Total (without water)59,10911
Polymers58,9789
Non-polymers1312
Water18010
1
A: CD59 glycoprotein
C: CD59 glycoprotein
G: Cyclic peptide CP-06
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,7254
Polymers19,6593
Non-polymers651
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: CD59 glycoprotein
E: CD59 glycoprotein
J: Cyclic peptide CP-06


Theoretical massNumber of molelcules
Total (without water)19,6593
Polymers19,6593
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
D: CD59 glycoprotein
F: CD59 glycoprotein
H: Cyclic peptide CP-06
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,7254
Polymers19,6593
Non-polymers651
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)30.94, 85.88, 96.57
Angle α, β, γ (deg.)90, 90.03, 90
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21A
32A
42A
53A
63A
74A
84A
95A
105A
116A
126A
137A
147A
158A
168A
179A
189A
1910A
2010A
2111A
2211A
2312A
2412A
2513A
2613A
2714A
2814A
2915A
3015A

NCS domain segments:

Beg auth comp-ID: MET / Beg label comp-ID: MET / Auth asym-ID: A / Label asym-ID: A

Dom-IDComponent-IDEns-IDEnd auth comp-IDEnd label comp-IDAuth seq-IDLabel seq-ID
111GLNGLN0 - 741 - 75
211GLNGLN0 - 741 - 75
322GLNGLN0 - 741 - 75
422GLNGLN0 - 741 - 75
533GLUGLU0 - 761 - 77
633GLUGLU0 - 761 - 77
744GLNGLN0 - 741 - 75
844GLNGLN0 - 741 - 75
955GLUGLU0 - 761 - 77
1055GLUGLU0 - 761 - 77
1166LEULEU0 - 751 - 76
1266LEULEU0 - 751 - 76
1377GLNGLN0 - 741 - 75
1477GLNGLN0 - 741 - 75
1588LEULEU0 - 751 - 76
1688LEULEU0 - 751 - 76
1799GLNGLN0 - 741 - 75
1899GLNGLN0 - 741 - 75
191010GLNGLN0 - 741 - 75
201010GLNGLN0 - 741 - 75
211111LEULEU0 - 751 - 76
221111LEULEU0 - 751 - 76
231212GLNGLN0 - 741 - 75
241212GLNGLN0 - 741 - 75
251313GLNGLN0 - 741 - 75
261313GLNGLN0 - 741 - 75
271414GLUGLU0 - 761 - 77
281414GLUGLU0 - 761 - 77
291515GLNGLN0 - 741 - 75
301515GLNGLN0 - 741 - 75

NCS ensembles :
IDDetails
1Local NCS retraints between domains: 1 2
2Local NCS retraints between domains: 3 4
3Local NCS retraints between domains: 5 6
4Local NCS retraints between domains: 7 8
5Local NCS retraints between domains: 9 10
6Local NCS retraints between domains: 11 12
7Local NCS retraints between domains: 13 14
8Local NCS retraints between domains: 15 16
9Local NCS retraints between domains: 17 18
10Local NCS retraints between domains: 19 20
11Local NCS retraints between domains: 21 22
12Local NCS retraints between domains: 23 24
13Local NCS retraints between domains: 25 26
14Local NCS retraints between domains: 27 28
15Local NCS retraints between domains: 29 30

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Components

#1: Protein
CD59 glycoprotein / 1F5 antigen / 20 kDa homologous restriction factor / HRF-20 / HRF20 / MAC-inhibitory protein / MAC- ...1F5 antigen / 20 kDa homologous restriction factor / HRF-20 / HRF20 / MAC-inhibitory protein / MAC-IP / MEM43 antigen / Membrane attack complex inhibition factor / MACIF / Membrane inhibitor of reactive lysis / MIRL / Protectin


Mass: 8987.199 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CD59, MIC11, MIN1, MIN2, MIN3, MSK21 / Production host: Escherichia coli (E. coli) / References: UniProt: P13987
#2: Protein/peptide Cyclic peptide CP-06


Mass: 1684.859 Da / Num. of mol.: 3 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)
#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 10 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

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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

CrystalDensity Matthews: 2.13 Å3/Da / Density % sol: 42.38 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7 / Details: 0.01 M ZnCl2, 0.1 M HEPES pH 7.0, 20% w/v PEG 6000

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Jul 10, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.43→48.332 Å / Num. obs: 18920 / % possible obs: 99.1 % / Redundancy: 3.4 % / Biso Wilson estimate: 78.67 Å2 / CC1/2: 0.99 / Rmerge(I) obs: 0.102 / Rpim(I) all: 0.066 / Rrim(I) all: 0.122 / Net I/σ(I): 7
Reflection shellResolution: 2.43→2.47 Å / Rmerge(I) obs: 0.23 / Mean I/σ(I) obs: 0.7 / Num. unique obs: 1967 / CC1/2: 0.29 / Rpim(I) all: 0.143 / Rrim(I) all: 0.272 / % possible all: 99.5

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Processing

Software
NameVersionClassification
REFMAC5.8.0425refinement
xia2data reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.43→48.332 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.917 / SU B: 45.581 / SU ML: 0.436 / Cross valid method: FREE R-VALUE / ESU R: 0.908 / ESU R Free: 0.352
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2983 969 5.127 %
Rwork0.2353 17932 -
all0.239 --
obs-18901 98.948 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 78.563 Å2
Baniso -1Baniso -2Baniso -3
1--1.882 Å20 Å20.344 Å2
2--1.587 Å20 Å2
3---0.294 Å2
Refinement stepCycle: LAST / Resolution: 2.43→48.332 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3691 0 362 10 4063
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.0124168
X-RAY DIFFRACTIONr_bond_other_d0.0010.0163641
X-RAY DIFFRACTIONr_angle_refined_deg2.7771.8555662
X-RAY DIFFRACTIONr_angle_other_deg1.0611.7958396
X-RAY DIFFRACTIONr_dihedral_angle_1_deg8.6475453
X-RAY DIFFRACTIONr_dihedral_angle_2_deg20.707560
X-RAY DIFFRACTIONr_dihedral_angle_other_2_deg9.328584
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.89610646
X-RAY DIFFRACTIONr_dihedral_angle_6_deg13.72910201
X-RAY DIFFRACTIONr_chiral_restr0.1360.2597
X-RAY DIFFRACTIONr_gen_planes_refined0.010.024983
X-RAY DIFFRACTIONr_gen_planes_other0.0030.021041
X-RAY DIFFRACTIONr_nbd_refined0.2540.2845
X-RAY DIFFRACTIONr_symmetry_nbd_other0.2240.23424
X-RAY DIFFRACTIONr_nbtor_refined0.2060.21896
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0950.22454
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.2360.285
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.0490.21
X-RAY DIFFRACTIONr_metal_ion_refined0.2790.22
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.2230.222
X-RAY DIFFRACTIONr_nbd_other0.2410.2112
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.2960.25
X-RAY DIFFRACTIONr_mcbond_it7.4415.1861830
X-RAY DIFFRACTIONr_mcbond_other7.445.1871830
X-RAY DIFFRACTIONr_mcangle_it10.1099.2972277
X-RAY DIFFRACTIONr_mcangle_other10.1089.2992278
X-RAY DIFFRACTIONr_scbond_it8.6615.722338
X-RAY DIFFRACTIONr_scbond_other8.6615.7212338
X-RAY DIFFRACTIONr_scangle_it12.07710.3283385
X-RAY DIFFRACTIONr_scangle_other12.07510.3273386
X-RAY DIFFRACTIONr_lrange_it14.72454.9614401
X-RAY DIFFRACTIONr_lrange_other14.72454.9624400
X-RAY DIFFRACTIONr_ncsr_local_group_10.1070.052250
X-RAY DIFFRACTIONr_ncsr_local_group_20.1310.052206
X-RAY DIFFRACTIONr_ncsr_local_group_30.1110.052323
X-RAY DIFFRACTIONr_ncsr_local_group_40.1240.052236
X-RAY DIFFRACTIONr_ncsr_local_group_50.1370.052254
X-RAY DIFFRACTIONr_ncsr_local_group_60.1150.052277
X-RAY DIFFRACTIONr_ncsr_local_group_70.1040.052266
X-RAY DIFFRACTIONr_ncsr_local_group_80.110.052306
X-RAY DIFFRACTIONr_ncsr_local_group_90.1240.052205
X-RAY DIFFRACTIONr_ncsr_local_group_100.1180.052248
X-RAY DIFFRACTIONr_ncsr_local_group_110.1230.052262
X-RAY DIFFRACTIONr_ncsr_local_group_120.10.052272
X-RAY DIFFRACTIONr_ncsr_local_group_130.1350.052224
X-RAY DIFFRACTIONr_ncsr_local_group_140.1280.052281
X-RAY DIFFRACTIONr_ncsr_local_group_150.110.052218
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDRefine-IDTypeRms dev position (Å)Weight position
11AX-RAY DIFFRACTIONLocal ncs0.107030.05009
12AX-RAY DIFFRACTIONLocal ncs0.107030.05009
23AX-RAY DIFFRACTIONLocal ncs0.130840.0501
24AX-RAY DIFFRACTIONLocal ncs0.130840.0501
35AX-RAY DIFFRACTIONLocal ncs0.110790.0501
36AX-RAY DIFFRACTIONLocal ncs0.110790.0501
47AX-RAY DIFFRACTIONLocal ncs0.123770.0501
48AX-RAY DIFFRACTIONLocal ncs0.123770.0501
59AX-RAY DIFFRACTIONLocal ncs0.136610.05009
510AX-RAY DIFFRACTIONLocal ncs0.136610.05009
611AX-RAY DIFFRACTIONLocal ncs0.115370.0501
612AX-RAY DIFFRACTIONLocal ncs0.115370.0501
713AX-RAY DIFFRACTIONLocal ncs0.103570.0501
714AX-RAY DIFFRACTIONLocal ncs0.103570.0501
815AX-RAY DIFFRACTIONLocal ncs0.10980.0501
816AX-RAY DIFFRACTIONLocal ncs0.10980.0501
917AX-RAY DIFFRACTIONLocal ncs0.123880.0501
918AX-RAY DIFFRACTIONLocal ncs0.123880.0501
1019AX-RAY DIFFRACTIONLocal ncs0.118210.0501
1020AX-RAY DIFFRACTIONLocal ncs0.118210.0501
1121AX-RAY DIFFRACTIONLocal ncs0.122940.0501
1122AX-RAY DIFFRACTIONLocal ncs0.122940.0501
1223AX-RAY DIFFRACTIONLocal ncs0.09960.0501
1224AX-RAY DIFFRACTIONLocal ncs0.09960.0501
1325AX-RAY DIFFRACTIONLocal ncs0.134830.0501
1326AX-RAY DIFFRACTIONLocal ncs0.134830.0501
1427AX-RAY DIFFRACTIONLocal ncs0.128080.0501
1428AX-RAY DIFFRACTIONLocal ncs0.128080.0501
1529AX-RAY DIFFRACTIONLocal ncs0.109840.0501
1530AX-RAY DIFFRACTIONLocal ncs0.109840.0501
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRfactor allNum. reflection allFsc freeFsc work% reflection obs (%)WRfactor Rwork
2.43-2.4930.407720.37612990.37813760.8960.88599.63660.368
2.493-2.5610.409750.39313010.39413820.8610.88399.56580.39
2.561-2.6350.438610.36612460.36913150.8340.90799.39160.344
2.635-2.7160.409620.33412170.33712830.890.93599.68820.303
2.716-2.8050.394670.29112130.29512880.870.94799.37890.259
2.805-2.9030.401720.32411030.32911820.9010.93399.40780.299
2.903-3.0120.337600.28511210.28811880.920.94899.41080.26
3.012-3.1340.333490.26410680.26711290.9420.96198.93710.232
3.134-3.2730.303550.2269970.2310630.940.9798.96520.205
3.273-3.4320.247520.20510090.20710750.9580.97598.69770.191
3.432-3.6170.279380.2258980.2279560.9510.97297.9080.216
3.617-3.8350.324570.2178800.2239500.9340.97898.63160.213
3.835-4.0980.272360.2198070.2218660.9560.97197.34410.219
4.098-4.4240.332310.1958070.1998520.9280.97898.35680.207
4.424-4.8420.276490.1736660.1817240.9580.98498.75690.193
4.842-5.4060.185400.1866390.1866890.9840.98298.54860.206
5.406-6.230.306350.2255770.236200.9540.97698.70970.257
6.23-7.5980.403200.2294880.2355180.9520.97298.06950.269
7.598-10.6150.227250.2063740.2084050.9710.97798.51850.258
10.615-48.3320.376130.3232220.3262390.8760.9198.32640.421
Refinement TLS params.

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

IDL112)L122)L132)L222)L232)L332)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T112)T122)T132)T222)T232)T332)Origin x (Å)Origin y (Å)Origin z (Å)
10.55790.2331.35338.02311.21286.41090.0017-0.2399-0.20360.1167-0.3521-0.06790.0943-0.0690.35030.15940.0382-0.01590.20860.22610.3144-12.3847-12.1068-7.8774
22.97530.44590.49615.65420.36517.40310.0027-0.20070.1607-0.2435-0.103-0.0097-0.0529-0.12410.10030.0418-0.001-0.03270.21310.05920.0686-4.27832.526413.5324
32.8059-1.75280.09817.42880.81867.4178-0.05020.3394-0.5466-0.0150.04440.24630.45810.27670.00570.16620.0157-0.07270.0976-0.07020.1627-11.3756-18.8313-31.2555
41.8981-0.6234-0.75177.50370.22325.9140.1970.31260.3744-0.3329-0.2542-0.1443-0.0923-0.09030.05720.1658-0.0643-0.05010.13750.13130.1397-12.377711.2365-40.3847
55.291-0.8154-1.96574.97661.77158.4232-0.0163-0.0157-0.00170.4475-0.0603-0.15780.10150.050.07670.0633-0.052-0.04880.18710.10020.0664-3.6947-3.809236.8698
64.3851.5684-1.03557.40570.42848.87830.145-0.32610.67740.2234-0.08270.1427-0.36690.261-0.06230.1075-0.0214-0.05560.0286-0.0430.192-11.544317.6693-17.0518
Refinement TLS groupSelection: ALL

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