[English] 日本語
Yorodumi
- EMDB-66100: Structure of the cholesterol-bound human proline transporter puri... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-66100
TitleStructure of the cholesterol-bound human proline transporter purified in DDM buffer
Map data
Sample
  • Complex: PROT
    • Protein or peptide: Sodium-dependent proline transporter
  • Ligand: SODIUM ION
  • Ligand: CHLORIDE ION
  • Ligand: CHOLESTEROL
Keywordshuman proline transporter purified / 12 transmembrane helices / TRANSPORT PROTEIN
Function / homology
Function and homology information


proline:sodium symporter activity / L-proline transmembrane transporter activity / glycine import across plasma membrane / Creatine metabolism / proline transport / SLC-mediated transport of neurotransmitters / neurotransmitter transport / sodium ion transmembrane transport / synaptic membrane / protein catabolic process ...proline:sodium symporter activity / L-proline transmembrane transporter activity / glycine import across plasma membrane / Creatine metabolism / proline transport / SLC-mediated transport of neurotransmitters / neurotransmitter transport / sodium ion transmembrane transport / synaptic membrane / protein catabolic process / synapse / membrane / plasma membrane
Similarity search - Function
Sodium:neurotransmitter symporter family signature 2. / Sodium:neurotransmitter symporter family signature 1. / Sodium:neurotransmitter symporter / Sodium:neurotransmitter symporter superfamily / Sodium:neurotransmitter symporter family / Sodium:neurotransmitter symporter family profile.
Similarity search - Domain/homology
Sodium-dependent proline transporter
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.91 Å
AuthorsWu JX / Zhou Y / Wang NQ / Wang JQ
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32371266 China
CitationJournal: Nat Commun / Year: 2026
Title: Structural basis for the transport mechanism and cholesterol modulation of the human proline transporter.
Authors: Yue Zhou / Ningqin Wang / Jiaqi Wang / Xinrui Meng / Jing-Xiang Wu /
Abstract: L-proline, an amino acid, acts as a potent neuromodulator in the central nervous system, with its synaptic concentrations finely regulated by the high-affinity L-proline transporter (PROT). ...L-proline, an amino acid, acts as a potent neuromodulator in the central nervous system, with its synaptic concentrations finely regulated by the high-affinity L-proline transporter (PROT). Dysregulation of PROT function is implicated in neuropsychiatric disorders, yet its regulatory mechanisms remain poorly characterized. Here, we present high-resolution cryo-electron microscopy structures of human PROT in L-proline-free consensus and L-proline-bound states. The L-proline-bound structure reveals an occluded conformation, detailing the coordination of substrate and ions. Strikingly, our L-proline-free consensus structures capture an inward-open conformation with a cholesterol molecule bound directly within the substrate-binding site. Transport kinetics studies demonstrate that partial cholesterol depletion increases PROT's apparent affinity for L-proline, confirming that cholesterol inhibits L-proline uptake. Furthermore, we identify a conformationally sensitive site (CHOL1') present only in the inward-open conformation. This work elucidates PROT's transport cycle and demonstrates how cholesterol directly modulates neurotransmitter uptake, offering potential therapeutic strategies for brain disorders.
History
DepositionSep 3, 2025-
Header (metadata) releaseMar 25, 2026-
Map releaseMar 25, 2026-
UpdateAug 19, 2026-
Current statusAug 19, 2026Processing site: PDBc / Status: Released

-
Structure visualization

Supplemental images

emd_66100.png

Downloads & links

-
Map

FileDownload / File: emd_66100.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.07 Å/pix.
x 256 pix.
= 273.152 Å		1.07 Å/pix.
x 256 pix.
= 273.152 Å		1.07 Å/pix.
x 256 pix.
= 273.152 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.067 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.5
Minimum - Maximum-3.8958168 - 7.8036613
Average (Standard dev.)-0.0025274758 (±0.103317924)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 273.152 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_66100_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_66100_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : PROT

EntireName: PROT
Components
  • Complex: PROT
    • Protein or peptide: Sodium-dependent proline transporter
  • Ligand: SODIUM ION
  • Ligand: CHLORIDE ION
  • Ligand: CHOLESTEROL

-
Supramolecule #1: PROT

SupramoleculeName: PROT / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Sodium-dependent proline transporter

MacromoleculeName: Sodium-dependent proline transporter / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 70.960219 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKKLQGAHLR KPVTPDLLMT PSDQGDVDLD VDFAAHRGNW TGKLDFLLSC IGYCVGLGNV WRFPYRAYTN GGGAFLVPYF LMLAICGIP LFFLELSLGQ FSSLGPLAVW KISPLFKGAG AAMLLIVGLV AIYYNMIIAY VLFYLFASLT SDLPWEHCGN W WNTELCLE ...String:
MKKLQGAHLR KPVTPDLLMT PSDQGDVDLD VDFAAHRGNW TGKLDFLLSC IGYCVGLGNV WRFPYRAYTN GGGAFLVPYF LMLAICGIP LFFLELSLGQ FSSLGPLAVW KISPLFKGAG AAMLLIVGLV AIYYNMIIAY VLFYLFASLT SDLPWEHCGN W WNTELCLE HRVSKDGNGA LPLNLTCTVS PSEEYWSRYV LHIQGSQGIG SPGEIRWNLC LCLLLAWVIV FLCILKGVKS SG KVVYFTA TFPYLILLML LVRGVTLPGA WKGIQFYLTP QFHHLLSSKV WIEAALQIFY SLGVGFGGLL TFASYNTFHQ NIY RDTFIV TLGNAITSIL AGFAIFSVLG YMSQELGVPV DQVAKAGPGL AFVVYPQAMT MLPLSPFWSF LFFFMLLTLG LDSQ FAFLE TIVTAVTDEF PYYLRPKKAV FSGLICVAMY LMGLILTTDG GMYWLVLLDD YSASFGLMVV VITTCLAVTR VYGIQ RFCR DIHMMLGFKP GLYFRACWLF LSPATLLALM VYSIVKYQPS EYGSYRFPPW AELLGILMGL LSCLMIPAGM LVAVLR EEG SLWERLQQAS RPAMDWGPSL EENRTGMYVA TLAGSQSPKP LMVHMRKYGG ITSFENTAIE VDREIAEEEE SMM

UniProtKB: Sodium-dependent proline transporter

-
Macromolecule #2: SODIUM ION

MacromoleculeName: SODIUM ION / type: ligand / ID: 2 / Number of copies: 1
Molecular weightTheoretical: 22.99 Da

-
Macromolecule #3: CHLORIDE ION

MacromoleculeName: CHLORIDE ION / type: ligand / ID: 3 / Number of copies: 1 / Formula: CL
Molecular weightTheoretical: 35.453 Da

-
Macromolecule #4: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 4 / Number of copies: 6 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI POLARA 300
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: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Tecnai Polara / Image courtesy: FEI Company

+
Image processing

CTF correctionType: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.91 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 78503
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelChain - Source name: AlphaFold / Chain - Initial model type: in silico model
Output model

PDB-9wmp:
Structure of the cholesterol-bound human proline transporter purified in DDM buffer

+
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