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- PDB-8tq5: Crystal structure of Fab DX17 in complex with MHC-I (HLA-B*44:05) -

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Basic information

Entry
Database: PDB / ID: 8tq5
TitleCrystal structure of Fab DX17 in complex with MHC-I (HLA-B*44:05)
Components
  • Beta-2-microglobulin
  • Fab DX17 H-chain
  • Fab DX17 L-chain
  • HLA class I histocompatibility antigen B alpha chain (HLA-B*44:05)
  • MHC class II antigen
KeywordsIMMUNE SYSTEM / histocompatibility complex class I / MHC-I / immune response / immune system Fab / antibody / anti-MHC antibody / cancer tumor
Function / homology
Function and homology information


antigen processing and presentation / : / : / positive regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / negative regulation of receptor binding / DAP12 interactions / cellular response to iron ion / Endosomal/Vacuolar pathway ...antigen processing and presentation / : / : / positive regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / negative regulation of receptor binding / DAP12 interactions / cellular response to iron ion / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / peptide antigen assembly with MHC class II protein complex / cellular response to iron(III) ion / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / MHC class II protein complex / negative regulation of forebrain neuron differentiation / ER to Golgi transport vesicle membrane / peptide antigen assembly with MHC class I protein complex / regulation of erythrocyte differentiation / regulation of iron ion transport / MHC class I peptide loading complex / response to molecule of bacterial origin / HFE-transferrin receptor complex / T cell mediated cytotoxicity / antigen processing and presentation of endogenous peptide antigen via MHC class I / positive regulation of T cell cytokine production / antigen processing and presentation of exogenous peptide antigen via MHC class II / MHC class I protein complex / positive regulation of immune response / peptide antigen binding / negative regulation of neurogenesis / positive regulation of T cell mediated cytotoxicity / positive regulation of receptor-mediated endocytosis / multicellular organismal-level iron ion homeostasis / positive regulation of T cell activation / cellular response to nicotine / specific granule lumen / recycling endosome membrane / phagocytic vesicle membrane / positive regulation of cellular senescence / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / negative regulation of epithelial cell proliferation / Interferon gamma signaling / MHC class II protein complex binding / positive regulation of protein binding / Modulation by Mtb of host immune system / late endosome membrane / sensory perception of smell / tertiary granule lumen / DAP12 signaling / negative regulation of neuron projection development / iron ion transport / T cell differentiation in thymus / ER-Phagosome pathway / protein refolding / early endosome membrane / protein homotetramerization / amyloid fibril formation / intracellular iron ion homeostasis / learning or memory / immune response / Amyloid fiber formation / endoplasmic reticulum lumen / Golgi membrane / external side of plasma membrane / lysosomal membrane / focal adhesion / Neutrophil degranulation / SARS-CoV-2 activates/modulates innate and adaptive immune responses / structural molecule activity / endoplasmic reticulum / Golgi apparatus / protein homodimerization activity / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane / cytosol
Similarity search - Function
MHC class II, alpha chain, N-terminal / Class II histocompatibility antigen, alpha domain / Class II histocompatibility antigen, alpha domain / MHC class II, alpha/beta chain, N-terminal / MHC class I alpha chain, alpha1 alpha2 domains / Class I Histocompatibility antigen, domains alpha 1 and 2 / Beta-2-Microglobulin / : / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily ...MHC class II, alpha chain, N-terminal / Class II histocompatibility antigen, alpha domain / Class II histocompatibility antigen, alpha domain / MHC class II, alpha/beta chain, N-terminal / MHC class I alpha chain, alpha1 alpha2 domains / Class I Histocompatibility antigen, domains alpha 1 and 2 / Beta-2-Microglobulin / : / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily / MHC classes I/II-like antigen recognition protein / : / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Beta-2-microglobulin / MHC class I antigen / MHC class II antigen
Similarity search - Component
Biological speciesHomo sapiens (human)
Mus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsJiang, J. / Natarajan, K. / Boyd, L.F. / Margulies, D.H.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: To Be Published
Title: Crystal structure of Fab DX17 in complex with MHC-I (HLA-B*44:05)
Authors: Jiang, J. / Natarajan, K. / Boyd, L.F. / Margulies, D.H.
History
DepositionAug 6, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 5, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: HLA class I histocompatibility antigen B alpha chain (HLA-B*44:05)
B: Beta-2-microglobulin
P: MHC class II antigen
H: Fab DX17 H-chain
L: Fab DX17 L-chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,4666
Polymers92,2455
Non-polymers2211
Water3,549197
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area10100 Å2
ΔGint-43 kcal/mol
Surface area36420 Å2
Unit cell
Length a, b, c (Å)77.115, 104.427, 131.490
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

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Components

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Protein , 2 types, 2 molecules AB

#1: Protein HLA class I histocompatibility antigen B alpha chain (HLA-B*44:05)


Mass: 31802.119 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HLA-B / Plasmid: pET21b / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q860B7
#2: Protein Beta-2-microglobulin


Mass: 11879.356 Da / Num. of mol.: 1 / Fragment: UNP residues 21-119
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: B2M, CDABP0092, HDCMA22P / Plasmid: pET3a / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P61769

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Antibody , 2 types, 2 molecules HL

#4: Antibody Fab DX17 H-chain


Mass: 23629.586 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Cell (production host): Expi293F / Production host: Homo sapiens (human)
#5: Antibody Fab DX17 L-chain


Mass: 23843.357 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Plasmid: pCDNA3.1 / Cell (production host): Expi293F / Production host: Homo sapiens (human)

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Protein/peptide / Sugars / Non-polymers , 3 types, 199 molecules P

#3: Protein/peptide MHC class II antigen


Mass: 1090.165 Da / Num. of mol.: 1
Fragment: HLA-DPA1*02:01 derived peptide 77-85 (UNP residues 36-44)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HLA-DPA1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9TQB0
#6: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 197 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestN
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: 2.87 Å3/Da / Density % sol: 57.14 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6.5 / Details: 12% PEG20000, 0.1 M MES, pH 6.5

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Data collection

DiffractionMean temperature: 273 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jul 21, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.3→43.24 Å / Num. obs: 46944 / % possible obs: 97.9 % / Redundancy: 9 % / Biso Wilson estimate: 39.68 Å2 / CC1/2: 0.999 / CC star: 1 / Rmerge(I) obs: 0.083 / Rpim(I) all: 0.029 / Net I/σ(I): 17.6
Reflection shellResolution: 2.3→2.38 Å / Rmerge(I) obs: 1.5 / Mean I/σ(I) obs: 1.5 / Num. unique obs: 4508 / CC1/2: 0.61 / CC star: 0.87 / Rpim(I) all: 0.509 / % possible all: 95.5

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Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
PHENIX1.20.1_4487refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 7TUE
Resolution: 2.3→43.24 Å / SU ML: 0.2773 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 24.9624
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2344 2000 4.26 %
Rwork0.1927 44941 -
obs0.1945 46941 98.01 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 50.64 Å2
Refinement stepCycle: LAST / Resolution: 2.3→43.24 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6380 0 14 197 6591
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00346583
X-RAY DIFFRACTIONf_angle_d0.65318973
X-RAY DIFFRACTIONf_chiral_restr0.0488977
X-RAY DIFFRACTIONf_plane_restr0.00431164
X-RAY DIFFRACTIONf_dihedral_angle_d16.51342366
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.3-2.360.3411360.29423053X-RAY DIFFRACTION94.66
2.36-2.420.32031420.26453182X-RAY DIFFRACTION97.82
2.42-2.490.27021410.2483171X-RAY DIFFRACTION98.63
2.49-2.570.31521420.2513189X-RAY DIFFRACTION98.67
2.57-2.670.3081430.23953221X-RAY DIFFRACTION99.17
2.67-2.770.28581420.22613195X-RAY DIFFRACTION98.87
2.77-2.90.26691430.22173209X-RAY DIFFRACTION99.03
2.9-3.050.24721370.2193084X-RAY DIFFRACTION94.35
3.05-3.240.27571440.21853219X-RAY DIFFRACTION99.2
3.24-3.490.26491440.20093259X-RAY DIFFRACTION99.3
3.49-3.840.26431460.18883260X-RAY DIFFRACTION99.45
3.84-4.40.18731410.15653171X-RAY DIFFRACTION96.11
4.4-5.540.15621480.13863324X-RAY DIFFRACTION99.54
5.54-43.240.191510.17083404X-RAY DIFFRACTION97.45
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)
13.179310489480.227774782763-1.925896276713.14632922593-1.375830999826.13101748109-0.101391910715-0.090178321471-0.565008579805-0.369963439784-0.0931966492228-0.1270972726761.39121131880.263627395380.2182825702270.791721440341-0.0112945814469-0.09898554892710.358337991057-0.02982960402730.50915578156123.2003422718-2.2237905842719.3604887996
21.928297890020.599914426156-0.6956021329152.96613156771-3.200827101875.40177555015-0.2748702064150.396318532998-0.84655961279-1.330026937610.271925286573-0.1328950071241.8863838975-0.2153759136680.05206789428771.29589180752-0.0604388791444-0.03337210026410.512216765453-0.1935088035620.66809943192221.6298427673-5.879209865438.03626002149
31.836144489620.3752860017060.7739245063581.26909786109-0.8817220549123.37832958370.008135688422820.185633000961-0.196973490972-0.5275791688930.2030717637990.3340255223210.744443957589-0.709742101969-0.1290631695190.816963989285-0.201040672672-0.1881745494310.503650085071-0.04574579239160.58503515241711.32678017784.664640308999.73224779961
42.03943474601-0.1272134022880.6632867287086.841332856862.148695888232.33505834959-0.2967426460170.3785845751530.0195982627814-0.2209172041680.7184945971990.01286965364230.215823918918-0.0030434612739-0.3666403473770.332466593521-0.05274762138290.04202296254760.5268884120910.01576931073610.23699715340422.140253603217.301870679442.0880066183
51.42314706395-2.04377134658-0.2781375451617.582459533062.94660438794.340729984890.177452227322-0.1641424009850.00254581378463-0.471865416058-0.0184528163410.179439589323-0.144220098182-0.300780648586-0.1802924567030.20513532011-0.03719472744370.02528949018030.3287746677050.02495232047630.26855619623320.300200243424.049059705938.8052454992
63.37000566169-1.184211629851.131999061523.27888369339-3.303041760766.000892951740.1741245579740.287234662501-0.196477675391-0.4625022970930.0503248795848-0.02582858588521.134567379760.432209864212-0.2385946425080.3930405048330.03579101464310.004652683821020.295291020689-0.00814564594510.33171139401631.454142789917.360854382721.2929625748
74.096888812991.19249399398-0.4681864289887.73083805254-1.453558037225.805793564850.541147654466-0.801151752472-0.7010604559370.9379898673260.451794683493-0.002672732760810.609655041418-0.233509133109-1.18895508560.3923254248660.0643956266978-0.05444957369620.6362064545950.05635636158950.41850233081834.583832708510.052416474744.8506882859
83.88739617325-0.5071182027354.49542347591.85438576578-1.398632047835.441482769720.2263420125180.449670493255-0.218461432123-0.3186065064690.0232541695243-0.06027251002770.4518304923670.602308823714-0.1030823122280.4586240863930.0921267489942-0.02410531327250.316138473474-0.02598314403620.31269378784835.594698566210.733953272525.3721840641
98.083806637045.888735161953.333236409384.599956951581.633974012093.45461204520.234571436487-0.10738240778-1.64514549061-0.49757023363-0.151315822261-0.5889922607560.5812041937920.5158446892260.005674202327070.6780395873490.269272395902-0.04818063492210.608378841748-0.09589863342880.64315458994243.41366815195.5842786166329.189672001
105.11787498839-0.9687197720994.704816892422.53506893619-0.7766300940246.575314184690.231907104294-0.0687349253128-0.560528676755-0.4368108617970.162663804913-0.0267917101970.8963247096370.200548634519-0.3497051699620.5678333428260.0561642238762-0.02896760708130.313524036181-0.02085806307350.46900943022629.12797960148.15131045324.124885525
116.3710814064-3.551005898994.026869074363.47248478601-4.357159251156.108144607040.100747040789-0.5402502333370.394743660030.240967845829-0.321617009554-0.240921209878-0.963500093990.3479816140070.206746397150.489738820987-0.004957096835810.009935705285750.511391255032-0.1618039714750.58826069068245.93239746814.968740668942.7939477115
124.80805630751-0.1495637726324.481894444630.383490995224-0.1148114585194.101591826890.269724502530.8974585974850.14842552477-0.398415991530.155505163099-0.1921116732440.07570059823171.22080641676-0.1624005923630.4499185478980.1420913257360.06520596053930.6690510574990.06819984226130.30736325392741.190103780716.430456016220.8187113044
139.020570954911.13182115962-3.075750344368.51631958078-0.6331944606076.292386348690.2752974044890.1246819725531.27625371250.50311971817-0.4185377428180.114990771248-0.493387687984-0.3878085877190.1885610511880.3034499609440.02460893941280.0237712568930.394386347589-0.03177968183470.44075745654938.176221207119.67400806734.5311489813
142.607160891741.13247268269-2.738909908612.27747387428-3.832180980826.78790511843-0.1119753989681.1764333415-0.284594443050.01091300031220.382560187392-0.00375106559880.389508507541-0.233534735694-0.0919350213911.28302022758-0.264200313825-0.1773150279110.81368843716-0.1922761684420.62650250352413.6320908964-4.001797097248.06272769516
152.076085562420.0018148231451-0.5754848127623.4708804575-0.9490259129074.51029140044-0.1831487755460.002592448373360.299802009597-0.08572047598270.1535201376040.1526766606540.0900410862045-0.0707294954687-0.004136362383740.225610123001-0.0406590632512-0.09016946204840.2649550806410.006576803978540.25866213565420.348150624234.187566613719.8687034445
160.735989876303-1.19702979731-0.3443309532313.16804561696-1.155833493253.5931326239-0.08162952637030.09527218030370.0205462729739-0.09068003200660.04688293444450.11783002087-0.01174689024670.07171204423860.01185401419770.256708746553-0.0393568615114-0.1074913738370.2781235757890.0272730224780.28854773355720.059735565535.424046223713.32331755
171.723925732350.1024215775782.540441708772.96127402089-0.2054075549513.496464255230.1768127471050.340055052178-0.008775146395090.383643955656-0.27401006046-0.00226260124414-0.462928079351.049074578110.4112188724420.09901286324230.01820726450530.03474933082250.348598204085-0.07274766572080.30285944568721.585116555471.49236857174.52662356449
181.06965779436-0.7142853486472.143820497351.48512024386-1.822655747624.40752492823-0.0374807503823-0.0145806983916-0.191323206720.1298496904080.3571311929440.2343257766840.190048131024-0.86113164887-0.3118301678230.1905542601640.0009566482141090.0440229211350.3876052125270.07808556762530.32807611515216.263604753467.74957658225.04944900854
190.115512614772-0.237859516284-0.1284592923814.73359038145-2.613802429544.54921412880.0568205971163-0.1537657437490.09029112259020.1877356416890.08347173233540.127892025817-0.0176236117698-0.435447418854-0.0992760426630.108013411708-0.01350395655220.00224318393760.3902417144910.03767900907450.2813969291616.196133834768.96376094912.12260658858
201.461261811650.292251069124-0.6155883920233.67938018677-3.353182499813.15432374831-0.0167037728520.1438916102630.5161409894261.409525473680.525262625547-0.175025832253-0.965217839141-0.180903403117-0.4791354776350.3337888973830.05743648574380.06772282297350.510433656122-0.08083932995240.5154616812114.982542254477.71217973846.40009277223
212.07854630202-0.6092437180380.2165611075952.8869906683-1.331836000213.37775634277-0.004614712489650.332949811021-0.0966269321821-0.639362373902-0.03693578247770.2966073874950.669037570543-0.05050855962340.04541658589820.540556955906-0.0883768659232-0.1134411163030.360842177282-0.03173421812410.28159032155521.345930686131.9539766146-5.24222492544
220.144426901847-0.08681609199210.01550043839770.833905650419-0.8795242050261.08825684970.0890772937781-0.07848492568850.0480423889869-0.238275848481-0.0621176806980.108090223420.247996517986-0.0334717313677-0.02620654130490.155780019413-0.0105287983419-0.04097333920150.407537373287-0.02522831209950.30044723256125.946571722157.2330029113-3.08162979071
231.383562968371.091980464711.719558818534.282137959351.788689117894.176467102160.0889677212202-0.0546277921626-0.02312686491190.06394055638070.00577553093478-0.3110399765170.09854642741690.325905082062-0.07994047077630.09546932253040.0111784441692-0.0059540820090.3629469168030.0160320647190.35132779434532.703391391868.1381092833-3.92658970735
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

IDRefine TLS-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11chain 'A' and (resid 1 through 56 )AA1 - 561 - 56
22chain 'A' and (resid 57 through 84 )AA57 - 8457 - 84
33chain 'A' and (resid 85 through 174 )AA85 - 17485 - 174
44chain 'A' and (resid 175 through 197 )AA175 - 197175 - 197
55chain 'A' and (resid 198 through 267 )AA198 - 267198 - 267
66chain 'B' and (resid 0 through 11 )BB0 - 111 - 12
77chain 'B' and (resid 12 through 19 )BB12 - 1913 - 20
88chain 'B' and (resid 20 through 41 )BB20 - 4121 - 42
99chain 'B' and (resid 42 through 51 )BB42 - 5143 - 52
1010chain 'B' and (resid 52 through 71 )BB52 - 7153 - 72
1111chain 'B' and (resid 72 through 77 )BB72 - 7773 - 78
1212chain 'B' and (resid 78 through 90 )BB78 - 9079 - 91
1313chain 'B' and (resid 91 through 99 )BB91 - 9992 - 100
1414chain 'P' and (resid 1 through 9 )PC1 - 91 - 9
1515chain 'H' and (resid 1 through 82 )HD1 - 821 - 82
1616chain 'H' and (resid 83 through 116 )HD83 - 11683 - 116
1717chain 'H' and (resid 117 through 141 )HD117 - 141117 - 141
1818chain 'H' and (resid 142 through 164 )HD142 - 164142 - 164
1919chain 'H' and (resid 165 through 209 )HD165 - 209165 - 209
2020chain 'H' and (resid 210 through 221 )HD210 - 221210 - 221
2121chain 'L' and (resid 1 through 90 )LF1 - 901 - 90
2222chain 'L' and (resid 91 through 144 )LF91 - 14491 - 144
2323chain 'L' and (resid 145 through 213 )LF145 - 213145 - 213

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