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- PDB-9cwm: Cryo-EM structure of human Low-density lipoprotein receptor-relat... -

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Basic information

Entry
Database: PDB / ID: 9cwm
TitleCryo-EM structure of human Low-density lipoprotein receptor-related protein 2
ComponentsLow-density lipoprotein receptor-related protein 2
KeywordsMEMBRANE PROTEIN / human / kidney / Low-density lipoprotein receptor-related protein 2 / LRP2
Function / homology
Function and homology information


Transport of RCbl within the body / diol metabolic process / positive regulation of oligodendrocyte progenitor proliferation / pulmonary artery morphogenesis / secondary heart field specification / positive regulation of lysosomal protein catabolic process / folate import across plasma membrane / cobalamin transport / protein transporter activity / ventricular compact myocardium morphogenesis ...Transport of RCbl within the body / diol metabolic process / positive regulation of oligodendrocyte progenitor proliferation / pulmonary artery morphogenesis / secondary heart field specification / positive regulation of lysosomal protein catabolic process / folate import across plasma membrane / cobalamin transport / protein transporter activity / ventricular compact myocardium morphogenesis / response to leptin / Vitamin D (calciferol) metabolism / low-density lipoprotein particle receptor activity / metal ion transport / transcytosis / vitamin D metabolic process / cranial skeletal system development / neuron projection arborization / coronary artery morphogenesis / insulin-like growth factor I binding / outflow tract septum morphogenesis / positive regulation of neurogenesis / cargo receptor activity / aorta development / ventricular septum development / amyloid-beta clearance / hormone binding / vagina development / negative regulation of BMP signaling pathway / forebrain development / transport across blood-brain barrier / retinoid metabolic process / Retinoid metabolism and transport / clathrin-coated pit / receptor-mediated endocytosis / endosome lumen / neural tube closure / phosphatidylinositol 3-kinase/protein kinase B signal transduction / brush border membrane / kidney development / sensory perception of sound / clathrin-coated endocytic vesicle membrane / cellular response to growth factor stimulus / SH3 domain binding / lipid metabolic process / endocytosis / male gonad development / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / protein transport / protein-folding chaperone binding / gene expression / lysosome / cell population proliferation / receptor complex / apical plasma membrane / axon / lysosomal membrane / external side of plasma membrane / dendrite / calcium ion binding / negative regulation of apoptotic process / endoplasmic reticulum / Golgi apparatus / extracellular exosome / plasma membrane
Similarity search - Function
: / LRP2-like, EGF-like domain / Complement Clr-like EGF 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 ...: / LRP2-like, EGF-like domain / Complement Clr-like EGF 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 / Legume lectin, beta chain, Mn/Ca-binding site / : / Calcium-binding EGF domain / Low-density lipoprotein (LDL) receptor class A, conserved site / LDL-receptor class A (LDLRA) domain signature. / LDL-receptor class A (LDLRA) domain profile. / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A repeat / LDL receptor-like superfamily / Six-bladed beta-propeller, TolB-like / Coagulation Factor Xa inhibitory site / EGF-type aspartate/asparagine hydroxylation site / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Aspartic acid and asparagine hydroxylation site. / 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 1. / EGF-like domain signature 2. / EGF-like domain
Similarity search - Domain/homology
Low-density lipoprotein receptor-related protein 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsZhang, Z. / Lyu, M.
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: Cryo-EM structure of human Low-density lipoprotein receptor-related protein 2
Authors: Zhang, Z. / Lyu, M.
History
DepositionJul 29, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 6, 2025Provider: repository / Type: Initial release
Revision 1.0Aug 6, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Aug 6, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Aug 6, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Low-density lipoprotein receptor-related protein 2
B: Low-density lipoprotein receptor-related protein 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)1,056,64537
Polymers1,045,0052
Non-polymers11,64035
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein Low-density lipoprotein receptor-related protein 2 / LRP-2 / Glycoprotein 330 / gp330 / Megalin


Mass: 522502.562 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P98164
#2: Polysaccharide
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 9
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{}}}LINUCSPDB-CARE
#3: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#4: 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.: 23 / 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
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Low-density lipoprotein receptor-related protein 2 / Type: COMPLEX / Entity ID: #1 / Source: NATURAL
Source (natural)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 81000 X / Nominal defocus max: 1500 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 40 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

EM softwareName: PHENIX / Version: 1.20.1_4487: / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 111811 / Symmetry type: POINT

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