4OZ1

Crystal structure of human CAPERalpha UHM bound to SF3b155 ULM5


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.74 Å
  • R-Value Free: 0.180 
  • R-Value Work: 0.143 
  • R-Value Observed: 0.147 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Cancer-relevant splicing factor CAPER alpha engages the essential splicing factor SF3b155 in a specific ternary complex.

Loerch, S.Maucuer, A.Manceau, V.Green, M.R.Kielkopf, C.L.

(2014) J Biol Chem 289: 17325-17337

  • DOI: https://doi.org/10.1074/jbc.M114.558825
  • Primary Citation of Related Structures:  
    4OZ0, 4OZ1

  • PubMed Abstract: 

    U2AF homology motifs (UHMs) mediate protein-protein interactions with U2AF ligand motifs (ULMs) of pre-mRNA splicing factors. The UHM-containing alternative splicing factor CAPERα regulates splicing of tumor-promoting VEGF isoforms, yet the molecular target of the CAPERα UHM is unknown. Here we present structures of the CAPERα UHM bound to a representative SF3b155 ULM at 1.7 Å resolution and, for comparison, in the absence of ligand at 2.2 Å resolution. The prototypical UHM/ULM interactions authenticate CAPERα as a bona fide member of the UHM family of proteins. We identify SF3b155 as the relevant ULM-containing partner of full-length CAPERα in human cell extracts. Isothermal titration calorimetry comparisons of the purified CAPERα UHM binding known ULM-containing proteins demonstrate that high affinity interactions depend on the presence of an intact, intrinsically unstructured SF3b155 domain containing seven ULM-like motifs. The interplay among bound CAPERα molecules gives rise to the appearance of two high affinity sites in the SF3b155 ULM-containing domain. In conjunction with the previously identified, UHM/ULM-mediated complexes of U2AF(65) and SPF45 with SF3b155, this work demonstrates the capacity of SF3b155 to offer a platform for coordinated recruitment of UHM-containing splicing factors.


  • Organizational Affiliation

    From the Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642 and.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-binding protein 39
A, B
115Homo sapiensMutation(s): 0 
Gene Names: CAPERCAPERalphaFSAP59HCC1RBM39RNPC2
UniProt & NIH Common Fund Data Resources
Find proteins for Q14498 (Homo sapiens)
Explore Q14498 
Go to UniProtKB:  Q14498
PHAROS:  Q14498
GTEx:  ENSG00000131051 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ14498
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Splicing factor 3B subunit 110Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for O75533 (Homo sapiens)
Explore O75533 
Go to UniProtKB:  O75533
PHAROS:  O75533
GTEx:  ENSG00000115524 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO75533
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.74 Å
  • R-Value Free: 0.180 
  • R-Value Work: 0.143 
  • R-Value Observed: 0.147 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.653α = 90
b = 52.41β = 90
c = 85.141γ = 90
Software Package:
Software NamePurpose
PROTEUM PLUSdata collection
PROTEUM PLUSdata scaling
PDB_EXTRACTdata extraction
PHENIXrefinement

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 StatesR01 GM070503

Revision History  (Full details and data files)

  • Version 1.0: 2014-05-14
    Type: Initial release
  • Version 1.1: 2014-10-01
    Changes: Database references
  • Version 1.2: 2015-01-14
    Changes: Database references
  • Version 1.3: 2017-09-20
    Changes: Author supporting evidence, Database references, Derived calculations, Other, Refinement description, Source and taxonomy, Structure summary
  • Version 1.4: 2019-12-25
    Changes: Author supporting evidence
  • Version 1.5: 2023-12-27
    Changes: Data collection, Database references, Derived calculations, Refinement description