8CX6

TPX2 Minimal Active Domain on Microtubules


Experimental Data Snapshot

  • Method: SOLID-STATE NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structural basis of protein condensation on microtubules underlying branching microtubule nucleation.

Guo, C.Alfaro-Aco, R.Zhang, C.Russell, R.W.Petry, S.Polenova, T.

(2023) Nat Commun 14: 3682-3682

  • DOI: https://doi.org/10.1038/s41467-023-39176-z
  • Primary Citation of Related Structures:  
    8CX6

  • PubMed Abstract: 

    Targeting protein for Xklp2 (TPX2) is a key factor that stimulates branching microtubule nucleation during cell division. Upon binding to microtubules (MTs), TPX2 forms condensates via liquid-liquid phase separation, which facilitates recruitment of microtubule nucleation factors and tubulin. We report the structure of the TPX2 C-terminal minimal active domain (TPX2 α5-α7 ) on the microtubule lattice determined by magic-angle-spinning NMR. We demonstrate that TPX2 α5-α7 forms a co-condensate with soluble tubulin on microtubules and binds to MTs between two adjacent protofilaments and at the intersection of four tubulin heterodimers. These interactions stabilize the microtubules and promote the recruitment of tubulin. Our results reveal that TPX2 α5-α7 is disordered in solution and adopts a folded structure on MTs, indicating that TPX2 α5-α7 undergoes structural changes from unfolded to folded states upon binding to microtubules. The aromatic residues form dense interactions in the core, which stabilize folding of TPX2 α5-α7 on microtubules. This work informs on how the phase-separated TPX2 α5-α7 behaves on microtubules and represents an atomic-level structural characterization of a protein that is involved in a condensate on cytoskeletal filaments.


  • Organizational Affiliation

    Department of Chemistry and Biochemistry, University of Delaware, Newark, DE, 19716, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Targeting protein for Xklp2-A240Xenopus laevisMutation(s): 0 
Gene Names: tpx2-a
UniProt
Find proteins for Q6NUF4 (Xenopus laevis)
Explore Q6NUF4 
Go to UniProtKB:  Q6NUF4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6NUF4
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLID-STATE NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

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 States1DP2GM123493
The Pew Charitable TrustsUnited States00027340
David and Lucile Packard FoundationUnited States201440376
National Science Foundation (NSF, United States)United StatesCHE-0959496
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesP30GM110758

Revision History  (Full details and data files)

  • Version 1.0: 2023-06-28
    Type: Initial release
  • Version 1.1: 2024-05-15
    Changes: Data collection, Database references