[English] 日本語
Yorodumi
- EMDB-26595: CryoEM structure of human LACTB filament -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-26595
TitleCryoEM structure of human LACTB filament
Map dataRefine3D map
Sample
  • Complex: LACTB
    • Protein or peptide: Serine beta-lactamase-like protein LACTB, mitochondrial
Function / homology
Function and homology information


Hydrolases; Acting on peptide bonds (peptidases) / regulation of lipid metabolic process / lipid metabolic process / peptidase activity / mitochondrion / proteolysis / identical protein binding / cytosol
Similarity search - Function
Beta-lactamase-related / Beta-lactamase / Beta-lactamase/transpeptidase-like
Similarity search - Domain/homology
Serine beta-lactamase-like protein LACTB, mitochondrial
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsBennett JA / Steward LR / Aydin H
Funding support United States, 1 items
OrganizationGrant numberCountry
Other government United States
CitationJournal: PLoS Biol / Year: 2022
Title: The structure of the human LACTB filament reveals the mechanisms of assembly and membrane binding.
Authors: Jeremy A Bennett / Lottie R Steward / Johannes Rudolph / Adam P Voss / Halil Aydin /
Abstract: Mitochondria are complex organelles that play a central role in metabolism. Dynamic membrane-associated processes regulate mitochondrial morphology and bioenergetics in response to cellular demand. ...Mitochondria are complex organelles that play a central role in metabolism. Dynamic membrane-associated processes regulate mitochondrial morphology and bioenergetics in response to cellular demand. In tumor cells, metabolic reprogramming requires active mitochondrial metabolism for providing key metabolites and building blocks for tumor growth and rapid proliferation. To counter this, the mitochondrial serine beta-lactamase-like protein (LACTB) alters mitochondrial lipid metabolism and potently inhibits the proliferation of a variety of tumor cells. Mammalian LACTB is localized in the mitochondrial intermembrane space (IMS), where it assembles into filaments to regulate the efficiency of essential metabolic processes. However, the structural basis of LACTB polymerization and regulation remains incompletely understood. Here, we describe how human LACTB self-assembles into micron-scale filaments that increase their catalytic activity. The electron cryo-microscopy (cryoEM) structure defines the mechanism of assembly and reveals how highly ordered filament bundles stabilize the active state of the enzyme. We identify and characterize residues that are located at the filament-forming interface and further show that mutations that disrupt filamentation reduce enzyme activity. Furthermore, our results provide evidence that LACTB filaments can bind lipid membranes. These data reveal the detailed molecular organization and polymerization-based regulation of human LACTB and provide new insights into the mechanism of mitochondrial membrane organization that modulates lipid metabolism.
History
DepositionApr 5, 2022-
Header (metadata) releaseDec 7, 2022-
Map releaseDec 7, 2022-
UpdateJan 11, 2023-
Current statusJan 11, 2023Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_26595.png

Downloads & links

-
Map

FileDownload / File: emd_26595.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationRefine3D map
Voxel sizeX=Y=Z: 0.8211 Å
Density
Contour LevelBy AUTHOR: 0.0042
Minimum - Maximum-0.012025551 - 0.023476535
Average (Standard dev.)8.085424e-06 (±0.0010279961)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 262.752 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_26595_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: Postprocess map

Fileemd_26595_additional_1.map
AnnotationPostprocess map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Refine3D half map 1

Fileemd_26595_half_map_1.map
AnnotationRefine3D half map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Refine3D half map 2

Fileemd_26595_half_map_2.map
AnnotationRefine3D half map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : LACTB

EntireName: LACTB
Components
  • Complex: LACTB
    • Protein or peptide: Serine beta-lactamase-like protein LACTB, mitochondrial

-
Supramolecule #1: LACTB

SupramoleculeName: LACTB / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all
Details: Uniprot ID: P83111 - HUMAN LACTB, Serine beta-lactamase-like protein LACTB, mitochondrial
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 510 KDa

-
Macromolecule #1: Serine beta-lactamase-like protein LACTB, mitochondrial

MacromoleculeName: Serine beta-lactamase-like protein LACTB, mitochondrial
type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO / EC number: Hydrolases; Acting on peptide bonds (peptidases)
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 51.318648 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString: APPCSRCFAR AIESSRDLLH RIKDEVGAPG IVVGVSVDGK EVWSEGLGYA DVENRVPCKP ETVMRIASIS KSLTMVALAK LWEAGKLDL DIPVQHYVPE FPEKEYEGEK VSVTTRLLIS HLSGIRHYEK DIKKVKEEKA YKALKMMKEN VAFEQEKEGK S NEKNDFTK ...String:
APPCSRCFAR AIESSRDLLH RIKDEVGAPG IVVGVSVDGK EVWSEGLGYA DVENRVPCKP ETVMRIASIS KSLTMVALAK LWEAGKLDL DIPVQHYVPE FPEKEYEGEK VSVTTRLLIS HLSGIRHYEK DIKKVKEEKA YKALKMMKEN VAFEQEKEGK S NEKNDFTK FKTEQENEAK CRNSKPGKKK NDFEQGELYL REKFENSIES LRLFKNDPLF FKPGSQFLYS TFGYTLLAAI VE RASGCKY LDYMQKIFHD LDMLTTVQEE NEPVIYNRAR FYVYNKKKRL VNTPYVDNSY KWAGGGFLST VGDLLKFGNA MLY GYQVGL FKNSNENLLP GYLKPETMVM MWTPVPNTEM SWDKEGKYAM AWGVVERKQT YGSCRKQRHY ASHTGGAVGA SSVL LVLPE ELDTETINNK VPPRGIIVSI ICNMQSVGLN STALKIALEF DKDRSD

-
Experimental details

-
Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statefilament

-
Sample preparation

Concentration0.3 mg/mL
BufferpH: 7.5
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average exposure time: 3.985 sec. / Average electron dose: 59.58 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: OTHER / Details: Featureless cylinder
Final angle assignmentType: NOT APPLICABLE
Final reconstructionApplied symmetry - Helical parameters - Δz: 21.582 Å
Applied symmetry - Helical parameters - Δ&Phi: -48.258 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.1) / Number images used: 248548
FSC plot (resolution estimation)

+
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