PDBsum entry 3sxl

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protein Protein-protein interface(s) links
RNA binding domain PDB id
Jmol PyMol
Protein chains
157 a.a. *
* Residue conservation analysis
PDB id:
Name: RNA binding domain
Title: Sex-lethal RNA recognition domains 1 and 2 from drosophila melanogaster
Structure: Protein (sex-lethal). Chain: a, b, c. Fragment: RNA binding domains 1 and 2 (residues 112-294 of full length). Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.70Å     R-factor:   0.221     R-free:   0.264
Authors: S.M.Crowder,R.Kanaar,D.C.Rio,T.C.Alber
Key ref:
S.M.Crowder et al. (1999). Absence of interdomain contacts in the crystal structure of the RNA recognition motifs of Sex-lethal. Proc Natl Acad Sci U S A, 96, 4892-4897. PubMed id: 10220389 DOI: 10.1073/pnas.96.9.4892
04-Apr-99     Release date:   27-Apr-99    
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Protein chains
Pfam   ArchSchema ?
P19339  (SXL_DROME) -  Protein sex-lethal
354 a.a.
157 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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


DOI no: 10.1073/pnas.96.9.4892 Proc Natl Acad Sci U S A 96:4892-4897 (1999)
PubMed id: 10220389  
Absence of interdomain contacts in the crystal structure of the RNA recognition motifs of Sex-lethal.
S.M.Crowder, R.Kanaar, D.C.Rio, T.Alber.
By binding specific RNA transcripts, the Sex-lethal protein (SXL) governs sexual differentiation and dosage compensation in Drosophila melanogaster. To investigate the basis for RNA binding specificity, we determined the crystal structure of the tandem RNA recognition motifs (RRMs) of SXL. Both RRMs adopt the canonical RRM fold, and the 10-residue, interdomain linker shows significant disorder. In contrast to the previously determined structure of the two-RRM fragment of heterogeneous nuclear ribonucleoprotein Al, SXL displays no interdomain contacts between RRMs. These results suggest that the SXL RRMs are flexibly tethered in solution, and RNA binding restricts the orientation of RRMs. Therefore, the observed specificity for single-stranded, U-rich sequences does not arise from a predefined, rigid architecture of the isolated SXL RRMs.
  Selected figure(s)  
Figure 1.
Fig. 1. Structure of the SXL RRM domains. (A) Sigma-A-weighted, 2F[o] F[c] electron density map contoured at 1 illustrates the quality of the map. Residues shown are Tyr-164-Phe-173. (B) Ribbon diagram of SXL RRM1+2. Residues left out of the model for lack of interpretable electron density include 111-123, 204-205 (interdomain linker), 276-282 ( 2- 4 loop of RRM2), and 290-294 (C terminus). RNP-1 and RNP-2 sequences are colored in magenta. (C) Electrostatic surface potential of SXLl+2 calculated with GRASP (blue = +5 kT > white = 0 kT > red = 5 kT). The absence of interdomain contacts in the SXL RRMl+2 crystal structure is evident. Based on the structures of the RNA complexes of UlA and U2B''/U2A', the most positive regions are likely RNA binding surfaces.
Figure 2.
Fig. 2. Relationship of RRM domains in SXL and hnRNP Al. (A) Ribbon diagrams of Sex-lethal (green) and hnRNP A1 (red) superimposed by using the secondary structural elements of RRM1 of each protein. In contrast to hnRNP A1 RRM2, RRM2 of SXL makes no contacts with RRM1 and differs in orientation from RRM2 of hnRNP A1 by a 92.5° rotation. (B) NMR chemical shift changes for SXL RRM1+2 upon binding the sequence r(GU[8]C) (35). (Left) SXL RRM1+2. (Right) RRM1+2 modeled with the RRM domains arranged as in an hnRNP Al. Chemical shift changes are colored as follows: blue (0-200 Hz), green (201-400 Hz), yellow (401-600 Hz), orange (601-800 Hz), and red (801-1000 Hz). Changes caused by RNA binding are concentrated along the interdomain linker and RNA binding surfaces.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20862284 S.Khoshnevis, P.Neumann, and R.Ficner (2010).
Crystal structure of the RNA recognition motif of yeast translation initiation factor eIF3b reveals differences to human eIF3b.
  PLoS One, 5, 0.
PDB codes: 3ns5 3ns6
19174564 P.H.Kuo, L.G.Doudeva, Y.T.Wang, C.K.Shen, and H.S.Yuan (2009).
Structural insights into TDP-43 in nucleic-acid binding and domain interactions.
  Nucleic Acids Res, 37, 1799-1808.
PDB code: 3d2w
18293956 D.Anunciado, M.Agumeh, B.L.Kormos, D.L.Beveridge, J.L.Knee, and A.M.Baranger (2008).
Characterization of the dynamics of an essential helix in the U1A protein by time-resolved fluorescence measurements.
  J Phys Chem B, 112, 6122-6130.  
18022637 P.Deka, M.E.Bucheli, C.Moore, S.Buratowski, and G.Varani (2008).
Structure of the yeast SR protein Npl3 and Interaction with mRNA 3'-end processing signals.
  J Mol Biol, 375, 136-150.
PDB codes: 2osq 2osr
17508423 F.A.Rahman, J.F.Ainscough, N.Copeland, and D.Coverley (2007).
Cancer-associated missplicing of exon 4 influences the subnuclear distribution of the DNA replication factor CIZ1.
  Hum Mutat, 28, 993.  
17391014 H.Xie, S.Vucetic, L.M.Iakoucheva, C.J.Oldfield, A.K.Dunker, V.N.Uversky, and Z.Obradovic (2007).
Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions.
  J Proteome Res, 6, 1882-1898.  
17188295 K.R.Thickman, E.A.Sickmier, and C.L.Kielkopf (2007).
Alternative conformations at the RNA-binding surface of the N-terminal U2AF(65) RNA recognition motif.
  J Mol Biol, 366, 703-710.
PDB code: 2hzc
15853797 C.Maris, C.Dominguez, and F.H.Allain (2005).
The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression.
  FEBS J, 272, 2118-2131.  
16094695 S.Ilin, A.Hoskins, O.Ohlenschläger, H.R.Jonker, H.Schwalbe, and J.Wöhnert (2005).
Domain reorientation and induced fit upon RNA binding: solution structure and dynamics of ribosomal protein L11 from Thermotoga maritima.
  Chembiochem, 6, 1611-1618.
PDB code: 2k3f
14976553 G.Dong, G.Chakshusmathi, S.L.Wolin, and K.M.Reinisch (2004).
Structure of the La motif: a winged helix domain mediates RNA binding via a conserved aromatic patch.
  EMBO J, 23, 1000-1007.
PDB code: 1s29
14730023 H.Banerjee, A.Rahn, B.Gawande, S.Guth, J.Valcarcel, and R.Singh (2004).
The conserved RNA recognition motif 3 of U2 snRNA auxiliary factor (U2AF 65) is essential in vivo but dispensable for activity in vitro.
  RNA, 10, 240-253.  
15181172 J.Delaunay, G.Le Mée, N.Ezzeddine, G.Labesse, C.Terzian, M.Capri, and O.Aït-Ahmed (2004).
The Drosophila Bruno paralogue Bru-3 specifically binds the EDEN translational repression element.
  Nucleic Acids Res, 32, 3070-3082.  
12626338 D.L.Black (2003).
Mechanisms of alternative pre-messenger RNA splicing.
  Annu Rev Biochem, 72, 291-336.  
12554879 H.Banerjee, A.Rahn, W.Davis, and R.Singh (2003).
Sex lethal and U2 small nuclear ribonucleoprotein auxiliary factor (U2AF65) recognize polypyrimidine tracts using multiple modes of binding.
  RNA, 9, 88-99.  
14532129 M.Grskovic, M.W.Hentze, and F.Gebauer (2003).
A co-repressor assembly nucleated by Sex-lethal in the 3'UTR mediates translational control of Drosophila msl-2 mRNA.
  EMBO J, 22, 5571-5581.  
11917013 J.Vitali, J.Ding, J.Jiang, Y.Zhang, A.R.Krainer, and R.M.Xu (2002).
Correlated alternative side chain conformations in the RNA-recognition motif of heterogeneous nuclear ribonucleoprotein A1.
  Nucleic Acids Res, 30, 1531-1538.
PDB code: 1l3k
12388766 P.Björk, G.Baurén, S.Jin, Y.G.Tong, T.R.Bürglin, U.Hellman, and L.Wieslander (2002).
A novel conserved RNA-binding domain protein, RBD-1, is essential for ribosome biogenesis.
  Mol Biol Cell, 13, 3683-3695.  
11179892 J.M.Pérez-Cañadillas, and G.Varani (2001).
Recent advances in RNA-protein recognition.
  Curr Opin Struct Biol, 11, 53-58.  
10679466 A.A.Antson (2000).
Single-stranded-RNA binding proteins.
  Curr Opin Struct Biol, 10, 87-94.  
10606651 L.S.Hatton, J.J.Eloranta, L.M.Figueiredo, Y.Takagaki, J.L.Manley, and K.O'Hare (2000).
The Drosophila homologue of the 64 kDa subunit of cleavage stimulation factor interacts with the 77 kDa subunit encoded by the suppressor of forked gene.
  Nucleic Acids Res, 28, 520-526.  
10734193 M.Inoue, Y.Muto, H.Sakamoto, and S.Yokoyama (2000).
NMR studies on functional structures of the AU-rich element-binding domains of Hu antigen C.
  Nucleic Acids Res, 28, 1743-1750.
PDB codes: 1d8z 1d9a
10856256 M.R.Conte, T.Grüne, J.Ghuman, G.Kelly, A.Ladas, S.Matthews, and S.Curry (2000).
Structure of tandem RNA recognition motifs from polypyrimidine tract binding protein reveals novel features of the RRM fold.
  EMBO J, 19, 3132-3141.
PDB code: 1qm9
10970864 N.K.Gray, J.M.Coller, K.S.Dickson, and M.Wickens (2000).
Multiple portions of poly(A)-binding protein stimulate translation in vivo.
  EMBO J, 19, 4723-4733.  
10449418 T.Ito, Y.Muto, M.R.Green, and S.Yokoyama (1999).
Solution structures of the first and second RNA-binding domains of human U2 small nuclear ribonucleoprotein particle auxiliary factor (U2AF(65)).
  EMBO J, 18, 4523-4534.
PDB codes: 1u2f 2u2f
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.