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PDBsum entry 1u1q

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protein dna_rna links
Transport protein/DNA PDB id
1u1q
Jmol
Contents
Protein chain
183 a.a. *
DNA/RNA
Waters ×165
* Residue conservation analysis
PDB id:
1u1q
Name: Transport protein/DNA
Title: Crystal structure of up1 complexed with d(ttagggtta(di)gg); a human telomeric repeat containing inosine
Structure: 5'-d( Tp Ap Gp Gp Gp Tp Tp Ap (Oip) Gp G)-3'. Chain: b. Engineered: yes. Heterogeneous nuclear ribonucleoprotein a1. Chain: a. Synonym: helix-destabilizing protein, single-strand binding protein, hnrnp core protein a1. Engineered: yes
Source: Synthetic: yes. Other_details: oligonucleotide d(ttagggtta (di) gg) based on human telomeric repeat d(ttaggg)n. Homo sapiens. Human. Organism_taxid: 9606. Gene: hnrpa1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PQS)
Resolution:
1.80Å     R-factor:   0.207     R-free:   0.258
Authors: J.C.Myers,Y.Shamoo
Key ref:
J.C.Myers and Y.Shamoo (2004). Human UP1 as a model for understanding purine recognition in the family of proteins containing the RNA recognition motif (RRM). J Mol Biol, 342, 743-756. PubMed id: 15342234 DOI: 10.1016/j.jmb.2004.07.029
Date:
15-Jul-04     Release date:   21-Sep-04    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P09651  (ROA1_HUMAN) -  Heterogeneous nuclear ribonucleoprotein A1
Seq:
Struc:
372 a.a.
183 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     nucleotide binding     2 terms  

 

 
DOI no: 10.1016/j.jmb.2004.07.029 J Mol Biol 342:743-756 (2004)
PubMed id: 15342234  
 
 
Human UP1 as a model for understanding purine recognition in the family of proteins containing the RNA recognition motif (RRM).
J.C.Myers, Y.Shamoo.
 
  ABSTRACT  
 
Heterogeneous ribonucleoprotein A1 (hnRNP A1) is a prototype for the family of eukaryotic RNA processing proteins containing the common RNA recognition motif (RRM). The region consisting of residues 1-195 of hnRNP A1 is referred to as UP1. This region has two RRMs and has a high affinity for both single-stranded RNA and the human telomeric repeat sequence d(TTAGGG)(n). We have used UP1's novel DNA binding to investigate how RRMs bind nucleic acid bases through their highly conserved RNP consensus sequences. Nine complexes of UP1 bound to modified telomeric repeats were investigated using equilibrium fluorescence binding and X-ray crystallography. In two of the complexes, alteration of a guanine to either 2-aminopurine or nebularine resulted in an increase in K(d) from 88nM to 209nM and 316nM, respectively. The loss of these orienting interactions between UP1 and the substituted base allows it to flip between syn and anti conformations. Substitution of the same base with 7-deaza-guanine preserves the O6/N1 contacts but still increases the K(d) to 296nM and suggests that it is not simply the loss of affinity that gives rise to the base mobility, but also the stereochemistry of the specific contact to O6. Although these studies provide details of UP1 interactions to nucleic acids, three general observations about RRMs are also evident: (1) as suggested by informatic studies, main-chain to base hydrogen bonding makes up an important aspect of ligand recognition (2) steric clashes generated by modification of a hydrogen bond donor-acceptor pair to a donor-donor pair are poorly tolerated and (3) a conserved lysine position proximal to RNP-2 (K(106)-IFVGGI) orients the purine to allow stereochemical discrimination between adenine and guanine based on the 6-position. This single interaction is well-conserved in known RRM structures and appears to be a broad indicator for purine preference in the larger family of RRM proteins.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Guide to modified bases used in these studies. Adenine (ade), guanine (gua), 7-deaza-guanine (7deazaG), 7-deaza-adenine (7deazaA), nebularine (neb), inosine (ino), 2-aminopurine (2AP). Arrows indicate positions that are good hydrogen bond donors or acceptors. The nomenclature of each modified oligonucleotide starts with the base to be substituted, followed by its position from the 5' end of the sequence 5'-d(TTAGGGTTAGGG)-3', and then by the base substitution.
Figure 3.
Figure 3. Structures of UP1-oligonucleotide complexes for substitution of adenine 9. 2F[o] -F[c] composite omit electron density maps contoured at 1.25 s. Chevrons indicate the hydrogen bonding network. (a) Wild-type structure with Ade9 shown making hydrogen bonding contacts to the Arg178 guanidinium group through its N7 (2.7 Å) and from the main-chain carbonyl of Lys179 (3.0 Å). Ade9 is stacked directly over the conserved Phe108 of the RNP2 consensus sequence. (b) The UP1-A(9)Neb structure showed no substantive changes in either protein or DNA structures. The absence of the N6 amino group allowed the base to move slightly closer to Arg178 (2.5 Å). (c) UP1-A(9)7deazaA structure shows a large conformational rearrangement of the Arg178 side-chain. The Arg178 guanidinium group shifted 9.1 Å away from its position in the wild-type structure where it makes contacts to the O2 of Thy8 and N7 of Ade9 to make a new set of contacts to Glu93. All electron density Figures were made using PYMOL (DeLano Scientific, CA).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 342, 743-756) copyright 2004.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19710183 M.G.Rudolph, and D.Klostermeier (2009).
The Thermus thermophilus DEAD box helicase Hera contains a modified RNA recognition motif domain loosely connected to the helicase core.
  RNA, 15, 1993-2001.
PDB codes: 3i31 3i32
18289557 L.Li, H.Kang, P.Liu, N.Makkinje, S.T.Williamson, J.L.Leibowitz, and D.P.Giedroc (2008).
Structural lability in stem-loop 1 drives a 5' UTR-3' UTR interaction in coronavirus replication.
  J Mol Biol, 377, 790-803.  
18232056 X.W.Bian, J.P.Xu, Y.F.Ping, Y.Wang, J.H.Chen, C.P.Xu, Y.Z.Wu, J.Wu, X.D.Zhou, Y.S.Chen, J.Q.Shi, and J.M.Wang (2008).
Unique proteomic features induced by a potential antiglioma agent, Nordy (dl-nordihydroguaiaretic acid), in glioma cells.
  Proteomics, 8, 484-494.  
17284455 H.Tjong, and H.X.Zhou (2007).
DISPLAR: an accurate method for predicting DNA-binding sites on protein surfaces.
  Nucleic Acids Res, 35, 1465-1477.  
17997580 J.D.Ballin, S.Bharill, E.J.Fialcowitz-White, I.Gryczynski, Z.Gryczynski, and G.M.Wilson (2007).
Site-specific variations in RNA folding thermodynamics visualized by 2-aminopurine fluorescence.
  Biochemistry, 46, 13948-13960.  
17980039 Y.Benitex, and A.M.Baranger (2007).
Recognition of essential purines by the U1A protein.
  BMC Biochem, 8, 22.  
16966360 N.Morozova, J.Allers, J.Myers, and Y.Shamoo (2006).
Protein-RNA interactions: exploring binding patterns with a three-dimensional superposition analysis of high resolution structures.
  Bioinformatics, 22, 2746-2752.  
16982642 S.D.Auweter, F.C.Oberstrass, and F.H.Allain (2006).
Sequence-specific binding of single-stranded RNA: is there a code for recognition?
  Nucleic Acids Res, 34, 4943-4959.  
15659580 K.Moran-Jones, L.Wayman, D.D.Kennedy, R.R.Reddel, S.Sara, M.J.Snee, and R.Smith (2005).
hnRNP A2, a potential ssDNA/RNA molecular adapter at the telomere.
  Nucleic Acids Res, 33, 486-496.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.