[English] 日本語
Yorodumi
- PDB-3m0c: The X-ray Crystal Structure of PCSK9 in Complex with the LDL receptor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3m0c
TitleThe X-ray Crystal Structure of PCSK9 in Complex with the LDL receptor
Components
  • (Proprotein convertase subtilisin/kexin type 9PCSK9) x 2
  • Low-density lipoprotein receptorLDL receptor
KeywordsPROTEIN BINDING / PROTEIN COMPLEX / BETA PROPELLER / CHOLESTEROL CLEARANCE / PCSK9 / LDLR / Autocatalytic cleavage / Cholesterol metabolism / Disease mutation / Disulfide bond / Glycoprotein / Hydrolase / Lipid metabolism / Phosphoprotein / Protease / Secreted / Serine protease / Steroid metabolism / Zymogen / Coated pit / EGF-like domain / Endocytosis / Host-virus interaction / LDL / Lipid transport / Membrane / Receptor / Transmembrane / Transport
Function / homology
Function and homology information


regulation of phosphatidylcholine catabolic process / plasma lipoprotein particle clearance / positive regulation of lysosomal protein catabolic process / very-low-density lipoprotein particle receptor activity / negative regulation of astrocyte activation / negative regulation of low-density lipoprotein particle receptor binding / negative regulation of receptor-mediated endocytosis involved in cholesterol transport / low-density lipoprotein particle receptor catabolic process / extrinsic component of external side of plasma membrane / receptor-mediated endocytosis involved in cholesterol transport ...regulation of phosphatidylcholine catabolic process / plasma lipoprotein particle clearance / positive regulation of lysosomal protein catabolic process / very-low-density lipoprotein particle receptor activity / negative regulation of astrocyte activation / negative regulation of low-density lipoprotein particle receptor binding / negative regulation of receptor-mediated endocytosis involved in cholesterol transport / low-density lipoprotein particle receptor catabolic process / extrinsic component of external side of plasma membrane / receptor-mediated endocytosis involved in cholesterol transport / negative regulation of microglial cell activation / very-low-density lipoprotein particle binding / PCSK9-LDLR complex / cholesterol import / negative regulation of receptor recycling / low-density lipoprotein particle clearance / clathrin heavy chain binding / PCSK9-AnxA2 complex / low-density lipoprotein particle receptor activity / negative regulation of sodium ion transmembrane transporter activity / apolipoprotein receptor binding / intestinal cholesterol absorption / positive regulation of triglyceride biosynthetic process / negative regulation of low-density lipoprotein particle clearance / low-density lipoprotein particle binding / response to caloric restriction / Chylomicron clearance / amyloid-beta clearance by cellular catabolic process / LDL clearance / positive regulation of low-density lipoprotein particle receptor catabolic process / lipoprotein metabolic process / signaling receptor inhibitor activity / high-density lipoprotein particle clearance / lipoprotein catabolic process / very-low-density lipoprotein particle receptor binding / regulation of protein metabolic process / low-density lipoprotein particle / phospholipid transport / cholesterol transport / negative regulation of low-density lipoprotein receptor activity / negative regulation of receptor internalization / endolysosome membrane / negative regulation of amyloid fibril formation / regulation of signaling receptor activity / sodium channel inhibitor activity / lysosomal transport / negative regulation of protein metabolic process / artery morphogenesis / triglyceride metabolic process / cellular response to fatty acid / regulation of cholesterol metabolic process / low-density lipoprotein particle receptor binding / COPII-coated ER to Golgi transport vesicle / amyloid-beta clearance / lipoprotein particle binding / sorting endosome / apolipoprotein binding / positive regulation of receptor internalization / cellular response to low-density lipoprotein particle stimulus / protein autoprocessing / Hydrolases; Acting on peptide bonds (peptidases); Serine endopeptidases / phospholipid metabolic process / long-term memory / phagocytosis / regulation of neuron apoptotic process / Retinoid metabolism and transport / clathrin-coated pit / somatodendritic compartment / VLDLR internalisation and degradation / cellular response to starvation / cholesterol metabolic process / neurogenesis / receptor-mediated endocytosis / liver development / cholesterol homeostasis / kidney development / Post-translational protein phosphorylation / clathrin-coated endocytic vesicle membrane / lipid metabolic process / neuron differentiation / positive regulation of inflammatory response / endocytosis / cellular response to insulin stimulus / positive regulation of neuron apoptotic process / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / : / late endosome / Cargo recognition for clathrin-mediated endocytosis / virus receptor activity / apical part of cell / Clathrin-mediated endocytosis / amyloid-beta binding / basolateral plasma membrane / protease binding / lysosome / molecular adaptor activity / receptor complex / early endosome / endosome membrane / lysosomal membrane
Similarity search - Function
Proprotein convertase subtilisin/kexin type 9, C-terminal domain 3 / Proprotein convertase subtilisin/kexin type 9, C-terminal domain 2 / Proprotein convertase subtilisin/kexin type 9, C-terminal domain 1 / Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain / Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain / Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain / Complement Clr-like EGF-like / Low-density lipoprotein receptor repeat class B / LDL-receptor class B (LDLRB) repeat profile. / LDLR class B repeat ...Proprotein convertase subtilisin/kexin type 9, C-terminal domain 3 / Proprotein convertase subtilisin/kexin type 9, C-terminal domain 2 / Proprotein convertase subtilisin/kexin type 9, C-terminal domain 1 / Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain / Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain / Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain / Complement Clr-like EGF-like / Low-density lipoprotein receptor repeat class B / LDL-receptor class B (LDLRB) repeat profile. / LDLR class B repeat / Low-density lipoprotein-receptor YWTD domain / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A, conserved site / LDL-receptor class A (LDLRA) domain signature. / LDL-receptor class A (LDLRA) domain profile. / Calcium-binding EGF domain / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A repeat / LDL receptor-like superfamily / Proteinase K-like catalytic domain / Six-bladed beta-propeller, TolB-like / Peptidase S8 propeptide/proteinase inhibitor I9 / Peptidase inhibitor I9 / Peptidase S8 propeptide/proteinase inhibitor I9 superfamily / Coagulation Factor Xa inhibitory site / Serine proteases, subtilase domain profile. / EGF-type aspartate/asparagine hydroxylation site / Peptidase S8, subtilisin-related / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Aspartic acid and asparagine hydroxylation site. / Peptidase S8/S53 domain superfamily / Subtilase family / Peptidase S8/S53 domain / EGF-like calcium-binding domain / Calcium-binding EGF-like domain / Epidermal growth factor-like domain. / EGF-like domain profile. / Growth factor receptor cysteine-rich domain superfamily / EGF-like domain signature 2. / EGF-like domain
Similarity search - Domain/homology
Low-density lipoprotein receptor / Proprotein convertase subtilisin/kexin type 9
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 7.01 Å
AuthorsSpraggon, G. / Hampton, E.N.
CitationJournal: To be Published
Title: The X-ray Crystal Structure of PCSK9 in Complex with the LDL receptor
Authors: Li, J. / Gavigan, J.A. / Zheng, G. / Huang, W. / Yowe, D. / Geisse, S. / Harris, J.L. / Lesley, S.A. / Spraggon, G.
History
DepositionMar 2, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 16, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Oct 13, 2021Group: Database references / Derived calculations
Category: database_2 / pdbx_struct_conn_angle ...database_2 / pdbx_struct_conn_angle / struct_conn / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.3Sep 6, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Proprotein convertase subtilisin/kexin type 9
B: Proprotein convertase subtilisin/kexin type 9
C: Low-density lipoprotein receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)160,1556
Polymers160,0343
Non-polymers1203
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)322.906, 322.906, 76.733
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number170
Space group name H-MP65

-
Components

#1: Protein Proprotein convertase subtilisin/kexin type 9 / PCSK9 / Proprotein convertase 9 / PC9 / Subtilisin/kexin-like protease PC9 / Neural apoptosis-regulated ...Proprotein convertase 9 / PC9 / Subtilisin/kexin-like protease PC9 / Neural apoptosis-regulated convertase 1 / NARC-1


Mass: 14019.734 Da / Num. of mol.: 1 / Fragment: PCSK9
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NARC1, PCSK9, PSEC0052 / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
References: UniProt: Q8NBP7, Hydrolases; Acting on peptide bonds (peptidases); Serine endopeptidases
#2: Protein Proprotein convertase subtilisin/kexin type 9 / PCSK9 / Proprotein convertase 9 / PC9 / Subtilisin/kexin-like protease PC9 / Neural apoptosis-regulated ...Proprotein convertase 9 / PC9 / Subtilisin/kexin-like protease PC9 / Neural apoptosis-regulated convertase 1 / NARC-1


Mass: 58320.707 Da / Num. of mol.: 1 / Fragment: PCSK9 / Mutation: D374Y
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NARC1, PCSK9, PSEC0052 / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
References: UniProt: Q8NBP7, Hydrolases; Acting on peptide bonds (peptidases); Serine endopeptidases
#3: Protein Low-density lipoprotein receptor / LDL receptor / LDL receptor


Mass: 87693.984 Da / Num. of mol.: 1 / Fragment: LDLR
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: LDLR / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P01130
#4: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Ca

-
Experimental details

-
Experiment

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

-
Sample preparation

Crystal growTemperature: 297 K / Method: vapor diffusion, sitting drop / pH: 8
Details: 1.4 M Ammonium phosphate, 0.2M sodium chloride in 0.1M Imidazole buffer, pH 8.0, VAPOR DIFFUSION, SITTING DROP, temperature 297K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.9775 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Apr 28, 2009 / Details: mirrors
RadiationMonochromator: graphite / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9775 Å / Relative weight: 1
ReflectionResolution: 7.01→279.645 Å / Num. all: 6162 / Num. obs: 6162 / % possible obs: 99.1 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 5.8 % / Rmerge(I) obs: 0.173 / Rsym value: 0.173 / Net I/σ(I): 3.2
Reflection shellResolution: 7.01→7.38 Å / Redundancy: 5.9 % / Rmerge(I) obs: 0.776 / Mean I/σ(I) obs: 0.6 / Rsym value: 0.776 / % possible all: 98.2

-
Processing

Software
NameVersionClassification
PHASERphasing
PHENIX(phenix.refine)refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entries 2QTW, 1IJQ

2qtw

1ijq


Resolution: 7.01→279.64 Å / SU ML: 4.32 / Isotropic thermal model: Overall / σ(F): 0 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.362 290 4.71 %
Rwork0.341 --
obs0.342 6162 82.2 %
all-6162 -
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 150 Å2 / ksol: 0.37 e/Å3
Displacement parametersBiso mean: 182.3 Å2
Refinement stepCycle: LAST / Resolution: 7.01→279.64 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7687 0 3 0 7690
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0197882
X-RAY DIFFRACTIONf_angle_d2.28610672
X-RAY DIFFRACTIONf_dihedral_angle_d18.8712831
X-RAY DIFFRACTIONf_chiral_restr0.1141210
X-RAY DIFFRACTIONf_plane_restr0.011396
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
7.01-8.8330.46241170.43632462X-RAY DIFFRACTION70
8.833-279.86770.33121730.30373410X-RAY DIFFRACTION94
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)
13.06280.74862.37161.0177-2.31981.4064-0.58311.1247-0.1768-0.2337-0.49080.25042.7757-1.17250.93741.6859-0.9557-0.05831.3633-0.07741.2087110.2597-121.9496-11.6892
27.7106-3.19663.93217.3903-5.34191.82340.31721.0338-0.5432.0134-0.10851.2071-1.00760.0639-0.26330.91990.35250.28410.0828-0.43761.1669119.6647-88.823-5.2715
3-0.73833.1055-1.87466.1691-2.12525.57970.57580.8807-1.130.4983-0.3753-0.0518-0.613-2.0143-0.9370.45310.22470.75082.0053-0.5671.9595122.2714-78.50276.6111
47.1262-4.75050.866.3338-1.12521.4971-2.3690.1623-1.52073.8255-0.31221.3081-0.5665-0.58911.47281.52460.3974-0.0922-0.2771-1.01121.5043127.9806-75.4454-8.8299
52.9263-2.4662-1.39954.3843.10144.9317-0.2212-0.1010.63810.74910.19860.29460.57510.58420.22521.2703-0.77010.00111.85030.23461.9947131.5864-105.3878-24.9053
6-3.0144-1.95532.92381.3553-0.3205-0.04530.18660.49910.96940.0473-1.9205-0.20980.64030.82170.6440.72220.11181.79482.29610.4711.8938159.6315-115.589-54.4792
71.0477-5.2112-0.69975.0242-5.16939.60210.10050.01281.38244.4141.2499-1.4318-4.7233-1.8071-0.70142.61010.75940.2639-0.02420.23670.8243139.4697-107.7534-50.1782
83.79794.52724.84297.36988.75523.0942-1.76672.43940.9009-2.17692.91691.0760.05021.7182-0.4741.3746-0.78840.50161.98910.94860.8665116.3659-120.7159-58.3216
98.66196.9655-4.47349.5691-2.71546.1769-3.38390.3888-1.2331-2.79121.5218-1.7023-0.9778-2.13991.54233.9613-0.44150.55950.94820.23730.3202107.7859-132.9647-53.3727
103.4468-0.1717-0.73232.26240.4551.0967-0.27430.95270.0741-1.43340.672-0.02781.43590.2117-0.47382.2442-0.9794-0.03391.22730.0880.341488.7392-144.4204-38.5468
112.4296-2.0249-0.7244.6439-1.77393.0346-0.7890.18370.82961.5834-1.1735-0.19390.7035-0.1015-1.48570.8366-0.8661-0.30631.26911.3306-1.007667.0893-139.0334-52.4328
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1CHAIN A
2X-RAY DIFFRACTION2CHAIN B AND RESID 452:531
3X-RAY DIFFRACTION3CHAIN B AND RESID 532:604
4X-RAY DIFFRACTION4CHAIN B AND RESID 605:692
5X-RAY DIFFRACTION5CHAIN B AND RESID 153:449
6X-RAY DIFFRACTION6CHAIN C AND (RESID 255:291 OR RESID 1003)
7X-RAY DIFFRACTION7CHAIN C AND (RESID 292:332 OR RESID 1001)
8X-RAY DIFFRACTION8CHAIN C AND (RESID 333:357 OR RESID 1002)
9X-RAY DIFFRACTION9CHAIN C AND RESID 358:376
10X-RAY DIFFRACTION10CHAIN C AND RESID 377:643
11X-RAY DIFFRACTION11CHAIN C AND RESID 644:692

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more