3PKN

Crystal structure of MLLE domain of poly(A) binding protein in complex with PAM2 motif of La-related protein 4 (LARP4)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.227 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

La-Related Protein 4 Binds Poly(A), Interacts with the Poly(A)-Binding Protein MLLE Domain via a Variant PAM2w Motif, and Can Promote mRNA Stability.

Yang, R.Gaidamakov, S.A.Xie, J.Lee, J.Martino, L.Kozlov, G.Crawford, A.K.Russo, A.N.Conte, M.R.Gehring, K.Maraia, R.J.

(2011) Mol Cell Biol 31: 542-556

  • DOI: https://doi.org/10.1128/MCB.01162-10
  • Primary Citation of Related Structures:  
    3PKN

  • PubMed Abstract: 

    The conserved RNA binding protein La recognizes UUU-3'OH on its small nuclear RNA ligands and stabilizes them against 3'-end-mediated decay. We report that newly described La-related protein 4 (LARP4) is a factor that can bind poly(A) RNA and interact with poly(A) binding protein (PABP). Yeast two-hybrid analysis and reciprocal immunoprecipitations (IPs) from HeLa cells revealed that LARP4 interacts with RACK1, a 40S ribosome- and mRNA-associated protein. LARP4 cosediments with 40S ribosome subunits and polyribosomes, and its knockdown decreases translation. Mutagenesis of the RNA binding or PABP interaction motifs decrease LARP4 association with polysomes. Several translation and mRNA metabolism-related proteins use a PAM2 sequence containing a critical invariant phenylalanine to make direct contact with the MLLE domain of PABP, and their competition for the MLLE is thought to regulate mRNA homeostasis. Unlike all ∼150 previously analyzed PAM2 sequences, LARP4 contains a variant PAM2 (PAM2w) with tryptophan in place of the phenylalanine. Binding and nuclear magnetic resonance (NMR) studies have shown that a peptide representing LARP4 PAM2w interacts with the MLLE of PABP within the affinity range measured for other PAM2 motif peptides. A cocrystal of PABC bound to LARP4 PAM2w shows tryptophan in the pocket in PABC-MLLE otherwise occupied by phenylalanine. We present evidence that LARP4 expression stimulates luciferase reporter activity by promoting mRNA stability, as shown by mRNA decay analysis of luciferase and cellular mRNAs. We propose that LARP4 activity is integrated with other PAM2 protein activities by PABP as part of mRNA homeostasis.


  • Organizational Affiliation

    31 Center Drive, Bldg. 31, Room 2A25, Bethesda, MD 20892-2426, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Polyadenylate-binding protein 188Homo sapiensMutation(s): 0 
Gene Names: PABPC1PAB1PABP1PABPC2
UniProt & NIH Common Fund Data Resources
Find proteins for P11940 (Homo sapiens)
Explore P11940 
Go to UniProtKB:  P11940
PHAROS:  P11940
GTEx:  ENSG00000070756 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11940
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
La-related protein 414N/AMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q71RC2 (Homo sapiens)
Explore Q71RC2 
Go to UniProtKB:  Q71RC2
PHAROS:  Q71RC2
GTEx:  ENSG00000161813 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ71RC2
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.227 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.91α = 90
b = 31.384β = 104.95
c = 52.647γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-01-12
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description