2MVL

Solution structure of cytosolic part of Trop2


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 20 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

The cytosolic tail of the tumor marker protein Trop2--a structural switch triggered by phosphorylation.

Pavsic, M.Ilc, G.Vidmar, T.Plavec, J.Lenarcic, B.

(2015) Sci Rep 5: 10324-10324

  • DOI: https://doi.org/10.1038/srep10324
  • Primary Citation of Related Structures:  
    2MVK, 2MVL

  • PubMed Abstract: 

    Trop2 is a transmembrane signaling glycoprotein upregulated in stem and carcinoma cells. Proliferation-enhancing signaling involves regulated intramembrane proteolytic release of a short cytoplasmic fragment, which is later engaged in a cytosolic signaling complex. We propose that Trop2 function is modulated by phosphorylation of a specific serine residue within this cytosolic region (Ser303), and by proximity effects exerted on the cytosolic tail by Trop2 dimerization. Structural characterization of both the transmembrane (Trop2TM) and cytosolic regions (Trop2IC) support this hypothesis, and shows that the central region of Trop2IC forms an α-helix. Comparison of NMR structures of non-phosphorylated and phosphorylated forms suggest that phosphorylation of Trop2IC triggers salt bridge reshuffling, resulting in significant conformational changes including ordering of the C-terminal tail. In addition, we demonstrate that the cytosolic regions of two Trop2 subunits can be brought into close proximity via transmembrane part dimerization. Finally, we show that Ser303-phosphorylation significantly affects the structure and accessibility of functionally important regions of the cytosolic tail. These observed structural features of Trop2 at the membrane-cytosol interface could be important for regulation of Trop2 signaling activity.


  • Organizational Affiliation

    Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tumor-associated calcium signal transducer 226Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P09758 (Homo sapiens)
Explore P09758 
Go to UniProtKB:  P09758
PHAROS:  P09758
GTEx:  ENSG00000184292 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP09758
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 20 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-05-06
    Type: Initial release
  • Version 1.1: 2018-04-18
    Changes: Data collection, Database references
  • Version 1.2: 2023-06-14
    Changes: Database references, Other
  • Version 1.3: 2024-05-15
    Changes: Data collection, Database references