6VP9

Cryo-EM structure of human NatB complex


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.46 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Molecular basis for N-terminal alpha-synuclein acetylation by human NatB.

Deng, S.Pan, B.Gottlieb, L.Petersson, J.Marmorstein, R.

(2020) Elife 9

  • DOI: https://doi.org/10.7554/eLife.57491
  • Primary Citation of Related Structures:  
    6VP9

  • PubMed Abstract: 

    NatB is one of three major N-terminal acetyltransferase (NAT) complexes (NatA-NatC), which co-translationally acetylate the N-termini of eukaryotic proteins. Its substrates account for about 21% of the human proteome, including well known proteins such as actin, tropomyosin, CDK2, and α-synuclein (αSyn). Human NatB (hNatB) mediated N-terminal acetylation of αSyn has been demonstrated to play key roles in the pathogenesis of Parkinson's disease and as a potential therapeutic target for hepatocellular carcinoma. Here we report the cryo-EM structure of hNatB bound to a CoA-αSyn conjugate, together with structure-guided analysis of mutational effects on catalysis. This analysis reveals functionally important differences with human NatA and Candida albicans NatB, resolves key hNatB protein determinants for αSyn N-terminal acetylation, and identifies important residues for substrate-specific recognition and acetylation by NatB enzymes. These studies have implications for developing small molecule NatB probes and for understanding the mode of substrate selection by NAT enzymes.


  • Organizational Affiliation

    Department of Chemistry, University of Pennsylvania, Philadelphia, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
N-alpha-acetyltransferase 20163Homo sapiensMutation(s): 0 
Gene Names: NAA20NAT5
EC: 2.3.1.254
UniProt & NIH Common Fund Data Resources
Find proteins for P61599 (Homo sapiens)
Explore P61599 
Go to UniProtKB:  P61599
PHAROS:  P61599
GTEx:  ENSG00000173418 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61599
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
N-alpha-acetyltransferase 25, NatB auxiliary subunit972Homo sapiensMutation(s): 0 
Gene Names: NAA25C12orf30MDM20NAP1
UniProt & NIH Common Fund Data Resources
Find proteins for Q14CX7 (Homo sapiens)
Explore Q14CX7 
Go to UniProtKB:  Q14CX7
PHAROS:  Q14CX7
GTEx:  ENSG00000111300 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ14CX7
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
MDVFM peptide5Escherichia coli K-12Mutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CMC (Subject of Investigation/LOI)
Query on CMC

Download Ideal Coordinates CCD File 
D [auth A]CARBOXYMETHYL COENZYME *A
C23 H38 N7 O18 P3 S
OBUOSIHPWVNVJN-GRFIIANRSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.46 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
MODEL REFINEMENTPHENIX1.17.1-3660
RECONSTRUCTIONRELION3.0

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR35 GM118090

Revision History  (Full details and data files)

  • Version 1.0: 2020-09-23
    Type: Initial release
  • Version 1.1: 2024-03-06
    Changes: Data collection, Database references