5SYF

High-resolution cryo-EM reconstruction of Taxol-stabilized microtubule

  • Classification: STRUCTURAL PROTEIN
  • Organism(s): Sus scrofa
  • Mutation(s): No 

  • Deposited: 2016-08-11 Released: 2017-02-01 
  • Deposition Author(s): Kellogg, E.H., Nogales, E.
  • Funding Organization(s): National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)

Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.50 Å
  • Aggregation State: HELICAL ARRAY 
  • Reconstruction Method: HELICAL 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Insights into the Distinct Mechanisms of Action of Taxane and Non-Taxane Microtubule Stabilizers from Cryo-EM Structures.

Kellogg, E.H.Hejab, N.M.Howes, S.Northcote, P.Miller, J.H.Diaz, J.F.Downing, K.H.Nogales, E.

(2017) J Mol Biol 429: 633-646

  • DOI: https://doi.org/10.1016/j.jmb.2017.01.001
  • Primary Citation of Related Structures:  
    5SYC, 5SYE, 5SYF, 5SYG

  • PubMed Abstract: 

    A number of microtubule (MT)-stabilizing agents (MSAs) have demonstrated or predicted potential as anticancer agents, but a detailed structural basis for their mechanism of action is still lacking. We have obtained high-resolution (3.9-4.2Å) cryo-electron microscopy (cryo-EM) reconstructions of MTs stabilized by the taxane-site binders Taxol and zampanolide, and by peloruside, which targets a distinct, non-taxoid pocket on β-tubulin. We find that each molecule has unique distinct structural effects on the MT lattice structure. Peloruside acts primarily at lateral contacts and has an effect on the "seam" of heterologous interactions, enforcing a conformation more similar to that of homologous (i.e., non-seam) contacts by which it regularizes the MT lattice. In contrast, binding of either Taxol or zampanolide induces MT heterogeneity. In doubly bound MTs, peloruside overrides the heterogeneity induced by Taxol binding. Our structural analysis illustrates distinct mechanisms of these drugs for stabilizing the MT lattice and is of relevance to the possible use of combinations of MSAs to regulate MT activity and improve therapeutic potential.


  • Organizational Affiliation

    Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tubulin alpha chain437Sus scrofaMutation(s): 0 
UniProt
Find proteins for Q2XVP4 (Sus scrofa)
Explore Q2XVP4 
Go to UniProtKB:  Q2XVP4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ2XVP4
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Tubulin beta chain426Sus scrofaMutation(s): 0 
UniProt
Find proteins for P02554 (Sus scrofa)
Explore P02554 
Go to UniProtKB:  P02554
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP02554
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
TA1 BindingDB:  5SYF EC50: 520 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.50 Å
  • Aggregation State: HELICAL ARRAY 
  • Reconstruction Method: HELICAL 
EM Software:
TaskSoftware PackageVersion
MODEL REFINEMENTRosetta3.6
MODEL REFINEMENTREFMAC5.5
RECONSTRUCTIONFREALIGN9.09

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 StatesGM51487

Revision History  (Full details and data files)

  • Version 1.0: 2017-02-01
    Type: Initial release
  • Version 1.1: 2017-03-08
    Changes: Database references
  • Version 1.2: 2017-09-13
    Changes: Author supporting evidence, Data collection
  • Version 1.3: 2019-12-25
    Changes: Author supporting evidence
  • Version 1.4: 2024-03-06
    Changes: Data collection, Database references, Derived calculations