+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-37555 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | RD-hMRP5-inward open | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | RD-hMRP5-inward open / 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 / purine nucleotide transmembrane transporter activity / cAMP transport / heme transmembrane transporter activity / glutathione transmembrane transport ...purine nucleotide transport / macromolecule transmembrane transporter activity / cGMP transport / carbohydrate derivative transmembrane transporter activity / Hyaluronan biosynthesis and export / folate transmembrane transport / purine nucleotide transmembrane transporter activity / cAMP transport / heme transmembrane transporter activity / glutathione transmembrane transport / glutathione transmembrane transporter activity / heme 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 / Paracetamol ADME / xenobiotic transport / 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 | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.06 Å | |||||||||
Authors | Liu ZM / Huang Y | |||||||||
Funding support | China, 1 items
| |||||||||
Citation | Journal: 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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_37555.map.gz | 97 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-37555-v30.xml emd-37555.xml | 15.2 KB 15.2 KB | Display Display | EMDB header |
Images | emd_37555.png | 49.1 KB | ||
Filedesc metadata | emd-37555.cif.gz | 6.1 KB | ||
Others | emd_37555_half_map_1.map.gz emd_37555_half_map_2.map.gz | 95.5 MB 95.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-37555 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37555 | HTTPS FTP |
-Related structure data
Related structure data | 8wi2MC 8kciC 8wi0C 8wi3C 8wi4C 8wi5C M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_37555.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 0.855 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #2
File | emd_37555_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_37555_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : hMRP5-R delet inward-open
Entire | Name: hMRP5-R delet inward-open |
---|---|
Components |
|
-Supramolecule #1: hMRP5-R delet inward-open
Supramolecule | Name: hMRP5-R delet inward-open / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: ATP-binding cassette sub-family C member 5
Macromolecule | Name: 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 weight | Theoretical: 149.273797 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: TSKHQHPVDN AGLFSCMTFS WLSSLARVAH KKGELSMEDV WSLSKHESSD VNCRRLERLW QEELNEVGPD AASLRRVVWI FCRTRLILS IVCLMITQLA GFSGPAFMVK HLLEYTQATE SNLQYSLLLV LGLLLTEIVR SWSLALTWAL NYRTGVRLRG A ILTMAFKK ...String: TSKHQHPVDN AGLFSCMTFS WLSSLARVAH KKGELSMEDV WSLSKHESSD VNCRRLERLW QEELNEVGPD AASLRRVVWI FCRTRLILS IVCLMITQLA GFSGPAFMVK HLLEYTQATE SNLQYSLLLV LGLLLTEIVR SWSLALTWAL NYRTGVRLRG A ILTMAFKK ILKLKNIKEK SLGELINICS NDGQRMFEAA AVGSLLAGGP VVAILGMIYN VIILGPTGFL GSAVFILFYP AM MFASRLT AYFRRKCVAA TDERVQKMNE VLTYIKFIKM YAWVKAFSQS VQKIREEERR ILEKAGYFQS ITVGVAPIVV VIA SVVTFS VHMTLGFDLT AAQAFTVVTV FNSMTFALKV TPFSVKSLSE ASVAVDRFKS LFLMEEVHMI KNKPASPHIK IEMK NATLA WDSSHSSIQN SPKLTPKMKK DKRASRGKKE KVRQLQRTEH QAVLAEQKGH LLLDSDERPS PEEEEGKHIH LGHLR LQRT LHSIDLEIQE GKLVGICGSV GSGKTSLISA ILGQMTLLEG SIAISGTFAY VAQQAWILNA TLRDNILFGK EYDEER YNS VLNSCCLRPD LAILPSSDLT EIGERGANLS GGQRQRISLA RALYSDRSIY ILDDPLSALD AHVGNHIFNS AIRKHLK SK TVLFVTHQLQ YLVDCDEVIF MKEGCITERG THEELMNLNG DYATIFNNLL LGETPPVEIN SKKETSGSQK KSQDKGPK T GSVKKEKAVK PEEGQLVQLE EKGQGSVPWS VYGVYIQAAG GPLAFLVIMA LFMLNVGSTA FSTWWLSYWI KQGSGNTTV TRGNETSVSD SMKDNPHMQY YASIYALSMA VMLILKAIRG VVFVKGTLRA SSRLHDELFR RILRSPMKFF DTTPTGRILN RFSKDMDEV DVRLPFQAEM FIQNVILVFF CVGMIAGVFP WFLVAVGPLV ILFSVLHIVS RVLIRELKRL DNITQSPFLS H ITSSIQGL ATIHAYNKGQ EFLHRYQELL DDNQAPFFLF TCAMRWLAVR LDLISIALIT TTGLMIVLMH GQIPPAYAGL AI SYAVQLT GLFQFTVRLA SETEARFTSV ERINHYIKTL SLEAPARIKN KAPSPDWPQE GEVTFENAEM RYRENLPLVL KKV SFTIKP KEKIGIVGRT GSGKSSLGMA LFRLVELSGG CIKIDGVRIS DIGLADLRSK LSIIPQEPVL FSGTVRSNLD PFNQ YTEDQ IWDALERTHM KECIAQLPLK LESEVMENGD NFSVGERQLL CIARALLRHC KILILDEATA AMDTETDLLI QETIR EAFA DCTMLTIAHR LHTVLGSDRI MVLAQGQVVE FDTPSVLLSN DSSRFYAMFA UniProtKB: ATP-binding cassette sub-family C member 5 |
-Macromolecule #2: CYS-GLN-ASP-ALA-LEU-GLU-THR-ALA-ALA-ARG-ALA-GLU-GLY-LEU-SER-LEU-A...
Macromolecule | Name: CYS-GLN-ASP-ALA-LEU-GLU-THR-ALA-ALA-ARG-ALA-GLU-GLY-LEU-SER-LEU-ASP-ALA-SER type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 1.922057 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: CQDALETAAR AEGLSLDAS |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination 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 |
-Image processing
Startup model | Type of model: OTHER |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.06 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 420839 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |