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- EMDB-37556: ND-hMRP5-inward open -

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Open data


ID or keywords:

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Basic information

Entry
Database: EMDB / ID: EMD-37556
TitleND-hMRP5-inward open
Map data
Sample
  • Complex: hMRP5-ND inward-open
    • Protein or peptide: ATP-binding cassette sub-family C member 5
KeywordsND-hMRP5 / MEMBRANE PROTEIN
Function / homology
Function and homology information


purine nucleotide transport / macromolecule transmembrane transporter activity / cGMP transport / carbohydrate derivative transmembrane transporter activity / Hyaluronan biosynthesis and export / folate transmembrane transport / heme transmembrane transport / purine nucleotide transmembrane transporter activity / cAMP transport / heme transmembrane transporter activity ...purine nucleotide transport / macromolecule transmembrane transporter activity / cGMP transport / carbohydrate derivative transmembrane transporter activity / Hyaluronan biosynthesis and export / folate transmembrane transport / heme transmembrane transport / purine nucleotide transmembrane transporter activity / cAMP transport / heme transmembrane transporter activity / glutathione transmembrane transporter activity / glutathione transmembrane transport / hyaluronan biosynthetic process / ATPase-coupled inorganic anion transmembrane transporter activity / organic anion transmembrane transporter activity / xenobiotic transmembrane transport / export across plasma membrane / ABC-type xenobiotic transporter / xenobiotic transport / Paracetamol ADME / ABC-type xenobiotic transporter activity / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / Azathioprine ADME / efflux transmembrane transporter activity / xenobiotic transmembrane transporter activity / transport across blood-brain barrier / ATPase-coupled transmembrane transporter activity / xenobiotic metabolic process / ABC-family proteins mediated transport / transmembrane transport / Golgi lumen / basolateral plasma membrane / endosome membrane / apical plasma membrane / ATP hydrolysis activity / ATP binding / membrane / plasma membrane
Similarity search - Function
ABC transporter transmembrane region / ABC transporter type 1, transmembrane domain / ABC transporter integral membrane type-1 fused domain profile. / ABC transporter type 1, transmembrane domain superfamily / ABC transporter-like, conserved site / ABC transporters family signature. / ABC transporter / ABC transporter-like, ATP-binding domain / ATP-binding cassette, ABC transporter-type domain profile. / ATPases associated with a variety of cellular activities ...ABC transporter transmembrane region / ABC transporter type 1, transmembrane domain / ABC transporter integral membrane type-1 fused domain profile. / ABC transporter type 1, transmembrane domain superfamily / ABC transporter-like, conserved site / ABC transporters family signature. / ABC transporter / ABC transporter-like, ATP-binding domain / ATP-binding cassette, ABC transporter-type domain profile. / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
ATP-binding cassette sub-family C member 5
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.38 Å
AuthorsLiu ZM / Huang Y
Funding support China, 1 items
OrganizationGrant numberCountry
National Science Foundation (NSF, China) China
CitationJournal: Nat Commun / Year: 2024
Title: Inhibition and transport mechanisms of the ABC transporter hMRP5.
Authors: Ying Huang / Chenyang Xue / Ruiqian Bu / Cang Wu / Jiachen Li / Jinqiu Zhang / Jinyu Chen / Zhaoying Shi / Yonglong Chen / Yong Wang / Zhongmin Liu /
Abstract: Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, ...Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment. Guided by these molecular insights, we design an inhibitory peptide that could block substrate entry into the transport pathway. We also identify a regulatory motif, comprising a positively charged cluster and hydrophobic patches, within the first nucleotide-binding domain that modulates hMRP5 localization by engaging with membranes. By integrating our structural, biochemical, computational, and cell biological findings, we propose a model for hMRP5 conformational cycling and localization. Overall, this work provides mechanistic understanding of hMRP5 function, while informing future selective hMRP5 inhibitor development. More broadly, this study advances our understanding of the structural dynamics and inhibition of ABC transporters.
History
DepositionSep 24, 2023-
Header (metadata) releaseJul 3, 2024-
Map releaseJul 3, 2024-
UpdateJul 3, 2024-
Current statusJul 3, 2024Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_37556.png

Downloads & links

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Map

FileDownload / File: emd_37556.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.29 Å
Density
Contour LevelBy AUTHOR: 0.287
Minimum - Maximum-3.1547258 - 5.3090467
Average (Standard dev.)0.003922074 (±0.12398922)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions200200200
Spacing200200200
CellA=B=C: 258.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_37556_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_37556_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : hMRP5-ND inward-open

EntireName: hMRP5-ND inward-open
Components
  • Complex: hMRP5-ND inward-open
    • Protein or peptide: ATP-binding cassette sub-family C member 5

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Supramolecule #1: hMRP5-ND inward-open

SupramoleculeName: hMRP5-ND inward-open / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: ATP-binding cassette sub-family C member 5

MacromoleculeName: ATP-binding cassette sub-family C member 5 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
EC number: Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 164.451391 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKDIDIGKEY IIPSPGYRSV RERTSTSGTH RDREDSKFRR TRPLECQDAL ETAARAEGLS LDASMHSQLR ILDEEHPKGK YHHGLSALK PIRTTSKHQH PVDNAGLFSC MTFSWLSSLA RVAHKKGELS MEDVWSLSKH ESSDVNCRRL ERLWQEELNE V GPDAASLR ...String:
MKDIDIGKEY IIPSPGYRSV RERTSTSGTH RDREDSKFRR TRPLECQDAL ETAARAEGLS LDASMHSQLR ILDEEHPKGK YHHGLSALK PIRTTSKHQH PVDNAGLFSC MTFSWLSSLA RVAHKKGELS MEDVWSLSKH ESSDVNCRRL ERLWQEELNE V GPDAASLR RVVWIFCRTR LILSIVCLMI TQLAGFSGPA FMVKHLLEYT QATESNLQYS LLLVLGLLLT EIVRSWSLAL TW ALNYRTG VRLRGAILTM AFKKILKLKN IKEKSLGELI NICSNDGQRM FEAAAVGSLL AGGPVVAILG MIYNVIILGP TGF LGSAVF ILFYPAMMFA SRLTAYFRRK CVAATDERVQ KMNEVLTYIK FIKMYAWVKA FSQSVQKIRE EERRILEKAG YFQS ITVGV APIVVVIASV VTFSVHMTLG FDLTAAQAFT VVTVFNSMTF ALKVTPFSVK SLSEASVAVD RFKSLFLMEE VHMIK NKPA SPHIKIEMKN ATLAWDSSHS SIQNSPKLTP KMKKDKRASR GKKEKVRQLQ RTEHQAVLAE QKGHLLLDSD ERPSPE EEE GKHIHLGHLR LQRTLHSIDL EIQEGKLVGI CGSVGSGKTS LISAILGQMT LLEGSIAISG TFAYVAQQAW ILNATLR DN ILFGKEYDEE RYNSVLNSCC LRPDLAILPS SDLTEIGERG ANLSGGQRQR ISLARALYSD RSIYILDDPL SALDAHVG N HIFNSAIRKH LKSKTVLFVT HQLQYLVDCD EVIFMKEGCI TERGTHEELM NLNGDYATIF NNLLLGETPP VEINSKKET SGSQKKSQDK GPKTGSVKKE KAVKPEEGQL VQLEEKGQGS VPWSVYGVYI QAAGGPLAFL VIMALFMLNV GSTAFSTWWL SYWIKQGSG NTTVTRGNET SVSDSMKDNP HMQYYASIYA LSMAVMLILK AIRGVVFVKG TLRASSRLHD ELFRRILRSP M KFFDTTPT GRILNRFSKD MDEVDVRLPF QAEMFIQNVI LVFFCVGMIA GVFPWFLVAV GPLVILFSVL HIVSRVLIRE LK RLDNITQ SPFLSHITSS IQGLATIHAY NKGQEFLHRY QELLDDNQAP FFLFTCAMRW LAVRLDLISI ALITTTGLMI VLM HGQIPP AYAGLAISYA VQLTGLFQFT VRLASETEAR FTSVERINHY IKTLSLEAPA RIKNKAPSPD WPQEGEVTFE NAEM RYREN LPLVLKKVSF TIKPKEKIGI VGRTGSGKSS LGMALFRLVE LSGGCIKIDG VRISDIGLAD LRSKLSIIPQ EPVLF SGTV RSNLDPFNQY TEDQIWDALE RTHMKECIAQ LPLKLESEVM ENGDNFSVGE RQLLCIARAL LRHCKILILD EATAAM DTE TDLLIQETIR EAFADCTMLT IAHRLHTVLG SDRIMVLAQG QVVEFDTPSV LLSNDSSRFY AMFAAAENKV AVKGLEG GG SGGGSWSHPQ FEKGARGGSG GGSWSHPQFE K

UniProtKB: ATP-binding cassette sub-family C member 5

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.2 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.38 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 865700
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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