PDBsum entry 1fht

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Ribonucleoprotein PDB id
Protein chain
116 a.a. *
* Residue conservation analysis
PDB id:
Name: Ribonucleoprotein
Title: RNA-binding domain of the u1a spliceosomal protein u1a117, nmr, 43 structures
Structure: U1 small nuclear ribonucleoprotein a. Chain: a. Fragment: n-terminal domain. Synonym: u1a117. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: human u1a 1-117. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 43 models
Authors: F.H.-T.Allain,C.C.Gubser,P.W.A.Howe,K.Nagai,D.Neuhaus, G.Varani
Key ref:
J.M.Avis et al. (1996). Solution structure of the N-terminal RNP domain of U1A protein: the role of C-terminal residues in structure stability and RNA binding. J Mol Biol, 257, 398-411. PubMed id: 8609632 DOI: 10.1006/jmbi.1996.0171
21-Feb-96     Release date:   11-Jul-96    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P09012  (SNRPA_HUMAN) -  U1 small nuclear ribonucleoprotein A
282 a.a.
116 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     nuclear mRNA splicing, via spliceosome   1 term 
  Biochemical function     nucleotide binding     3 terms  


DOI no: 10.1006/jmbi.1996.0171 J Mol Biol 257:398-411 (1996)
PubMed id: 8609632  
Solution structure of the N-terminal RNP domain of U1A protein: the role of C-terminal residues in structure stability and RNA binding.
J.M.Avis, F.H.Allain, P.W.Howe, G.Varani, K.Nagai, D.Neuhaus.
The solution structure of a fragment of the human U1A spliceosomal protein containing residues 2 to 117 (U1A117) determined using multi-dimensional heteronuclear NMR is presented. The C-terminal region of the molecule is considerably more ordered in the free protein than thought previously and its conformation is different from that seen in the crystal structure of the complex with U1 RNA hairpin II. The residues between Asp90 and Lys98 form an alpha-helix that lies across the beta-sheet, with residues IIe93, IIe94 and Met97 making contacts with Leu44, Phe56 and IIe58. This interaction prevents solvent exposure of hydrophobic residues on the surface of the beta-sheet, thereby stabilising the protein. Upon RNA binding, helix C moves away from this position, changing its orientation by 135 degrees to allow Tyr13, Phe56 and Gln54 to stack with bases of the RNA, and also allowing Leu44 to contact the RNA. The new position of helix C in the complex with RNA is stabilised by hydrophobic interactions from IIe93 and IIe94 to IIe58, Leu 41, Val62 and His 10, as well as a hydrogen bond between Ser91 and Thr11. The movement of helix C mainly involves changes in the main-chain torsion angles of Thr89, Asp90 and Ser91, the helix thereby acting as a "lid" over the RNA binding surface.
  Selected figure(s)  
Figure 2.
Figure 2. Diagonal plot of the NOE constraints used to calculate the structure of U1A117, as a function of sequence. Filled squares indicate one or more constraints between backbone atoms, filled triangles indicate one or more backbone to side-chain constraints, and open circles indicate one or more side-chain to side-chain constraints. Constraints defining the antiparallel b4-bl-b3-b2 sheet structure are indicated.
Figure 5.
Figure 5. Schematic representation of the U1A117 protein (shown only to residue 105), produced using the program MOLSCRIPT (Kraulis, 1991). The lowest energy structure from amongst the ensemble of 43 is shown.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1996, 257, 398-411) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21419778 D.Anunciado, A.Dhar, M.Gruebele, and A.M.Baranger (2011).
Multistep kinetics of the U1A-SL2 RNA complex dissociation.
  J Mol Biol, 408, 896-908.  
21113136 G.Weber, S.Trowitzsch, B.Kastner, R.Lührmann, and M.C.Wahl (2010).
Functional organization of the Sm core in the crystal structure of human U1 snRNP.
  EMBO J, 29, 4172-4184.
PDB code: 3pgw
19295135 A.Eulalio, F.Tritschler, R.Büttner, O.Weichenrieder, E.Izaurralde, and V.Truffault (2009).
The RRM domain in GW182 proteins contributes to miRNA-mediated gene silencing.
  Nucleic Acids Res, 37, 2974-2983.
PDB code: 2wbr
19447915 C.Netter, G.Weber, H.Benecke, and M.C.Wahl (2009).
Functional stabilization of an RNA recognition motif by a noncanonical N-terminal expansion.
  RNA, 15, 1305-1313.
PDB code: 3egn
18360780 Q.C.An, and G.Y.Liu (2009).
Molecular cloning, sequence identification, and tissue expression profile analysis of three novel porcine genes: SDHB, SNRPA and CRYBB1.
  Mol Biol Rep, 36, 683-690.  
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.  
18641416 T.Nagata, S.Suzuki, R.Endo, M.Shirouzu, T.Terada, M.Inoue, T.Kigawa, N.Kobayashi, P.Güntert, A.Tanaka, Y.Hayashizaki, Y.Muto, and S.Yokoyama (2008).
The RRM domain of poly(A)-specific ribonuclease has a noncanonical binding site for mRNA cap analog recognition.
  Nucleic Acids Res, 36, 4754-4767.
PDB code: 2rok
18790803 Y.Chen, J.Mandic, and G.Varani (2008).
Cell-free selection of RNA-binding proteins using in vitro compartmentalization.
  Nucleic Acids Res, 36, e128.  
17194603 B.L.Kormos, A.M.Baranger, and D.L.Beveridge (2007).
A study of collective atomic fluctuations and cooperativity in the U1A-RNA complex based on molecular dynamics simulations.
  J Struct Biol, 157, 500-513.  
17603075 B.L.Kormos, Y.Benitex, A.M.Baranger, and D.L.Beveridge (2007).
Affinity and specificity of protein U1A-RNA complex formation based on an additive component free energy model.
  J Mol Biol, 371, 1405-1419.  
17164477 M.G.Caprara, P.Chatterjee, A.Solem, K.L.Brady-Passerini, and B.J.Kaspar (2007).
An allosteric-feedback mechanism for protein-assisted group I intron splicing.
  RNA, 13, 211-222.  
16885237 C.Dominguez, and F.H.Allain (2006).
NMR structure of the three quasi RNA recognition motifs (qRRMs) of human hnRNP F and interaction studies with Bcl-x G-tract RNA: a novel mode of RNA recognition.
  Nucleic Acids Res, 34, 3634-3645.
PDB codes: 2hgl 2hgm 2hgn
16689644 H.Stark, and R.Lührmann (2006).
Cryo-electron microscopy of spliceosomal components.
  Annu Rev Biophys Biomol Struct, 35, 435-457.  
16407334 M.J.Law, M.E.Linde, E.J.Chambers, C.Oubridge, P.S.Katsamba, L.Nilsson, I.S.Haworth, and I.A.Laird-Offringa (2006).
The role of positively charged amino acids and electrostatic interactions in the complex of U1A protein and U1 hairpin II RNA.
  Nucleic Acids Res, 34, 275-285.  
16432215 M.J.Schellenberg, R.A.Edwards, D.B.Ritchie, O.A.Kent, M.M.Golas, H.Stark, R.Lührmann, J.N.Glover, and A.M.MacMillan (2006).
Crystal structure of a core spliceosomal protein interface.
  Proc Natl Acad Sci U S A, 103, 1266-1271.
PDB codes: 2f9d 2f9j
16698546 N.Dobson, G.Dantas, D.Baker, and G.Varani (2006).
High-resolution structural validation of the computational redesign of human U1A protein.
  Structure, 14, 847-856.
PDB code: 2a3j
16418270 R.C.Wilson, C.J.Bohlen, M.P.Foster, and C.E.Bell (2006).
Structure of Pfu Pop5, an archaeal RNase P protein.
  Proc Natl Acad Sci U S A, 103, 873-878.
PDB code: 2av5
16595295 S.C.Walker, and D.R.Engelke (2006).
Ribonuclease P: the evolution of an ancient RNA enzyme.
  Crit Rev Biochem Mol Biol, 41, 77.  
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.  
15914668 M.J.Law, E.J.Chambers, P.S.Katsamba, I.S.Haworth, and I.A.Laird-Offringa (2005).
Kinetic analysis of the role of the tyrosine 13, phenylalanine 56 and glutamine 54 network in the U1A/U1 hairpin II interaction.
  Nucleic Acids Res, 33, 2917-2928.  
16258832 N.Dobson, G.Dantas, and G.Varani (2005).
1H, 13C and 15N resonance assignments of URNdesign, a computationally redesigned RRM protein.
  J Biomol NMR, 33, 135.  
15951381 S.A.Showalter, and K.B.Hall (2005).
Correlated motions in the U1 snRNA stem/loop 2:U1A RBD1 complex.
  Biophys J, 89, 2046-2058.  
15857951 V.Calabro, M.D.Daugherty, and A.D.Frankel (2005).
A single intermolecular contact mediates intramolecular stabilization of both RNA and protein.
  Proc Natl Acad Sci U S A, 102, 6849-6854.
PDB code: 1zbn
15659359 V.Cojocaru, S.Nottrott, R.Klement, and T.M.Jovin (2005).
The snRNP 15.5K protein folds its cognate K-turn RNA: a combined theoretical and biochemical study.
  RNA, 11, 197-209.  
15753311 V.Guallar, and K.W.Borrelli (2005).
A binding mechanism in protein-nucleotide interactions: implication for U1A RNA binding.
  Proc Natl Acad Sci U S A, 102, 3954-3959.  
14988508 M.T.McClain, C.S.Lutz, K.M.Kaufman, O.Z.Faig, T.F.Gross, and J.A.James (2004).
Structural availability influences the capacity of autoantigenic epitopes to induce a widespread lupus-like autoimmune response.
  Proc Natl Acad Sci U S A, 101, 3551-3556.  
15192703 N.Leulliot, S.Quevillon-Cheruel, M.Graille, H.van Tilbeurgh, T.C.Leeper, K.S.Godin, T.E.Edwards, S.T.Sigurdsson, N.Rozenkrants, R.J.Nagel, M.Ares, and G.Varani (2004).
A new alpha-helical extension promotes RNA binding by the dsRBD of Rnt1p RNAse III.
  EMBO J, 23, 2468-2477.
PDB codes: 1t4n 1t4o
15341728 P.J.Simpson, T.P.Monie, A.Szendröi, N.Davydova, J.K.Tyzack, M.R.Conte, C.M.Read, P.D.Cary, D.I.Svergun, P.V.Konarev, S.Curry, and S.Matthews (2004).
Structure and RNA interactions of the N-terminal RRM domains of PTB.
  Structure, 12, 1631-1643.
PDB codes: 1sjq 1sjr
12842046 A.Jacks, J.Babon, G.Kelly, I.Manolaridis, P.D.Cary, S.Curry, and M.R.Conte (2003).
Structure of the C-terminal domain of human La protein reveals a novel RNA recognition motif coupled to a helical nuclear retention element.
  Structure, 11, 833-843.
PDB code: 1owx
12670951 C.Phillips, and S.Gunderson (2003).
Sequences adjacent to the 5' splice site control U1A binding upstream of the IgM heavy chain secretory poly(A) site.
  J Biol Chem, 278, 22102-22111.  
12809490 G.C.Pérez-Alvarado, M.Martínez-Yamout, M.M.Allen, R.Grosschedl, H.J.Dyson, and P.E.Wright (2003).
Structure of the nuclear factor ALY: insights into post-transcriptional regulatory and mRNA nuclear export processes.
  Biochemistry, 42, 7348-7357.
PDB code: 1no8
12773396 J.M.Pérez Cañadillas, and G.Varani (2003).
Recognition of GU-rich polyadenylation regulatory elements by human CstF-64 protein.
  EMBO J, 22, 2821-2830.
PDB code: 1p1t
12876372 P.B.Rupert, H.Xiao, and A.R.Ferré-D'Amaré (2003).
U1A RNA-binding domain at 1.8 A resolution.
  Acta Crystallogr D Biol Crystallogr, 59, 1521-1524.
PDB code: 1nu4
12637556 U.Kühn, A.Nemeth, S.Meyer, and E.Wahle (2003).
The RNA binding domains of the nuclear poly(A)-binding protein.
  J Biol Chem, 278, 16916-16925.  
12203842 C.S.Lutz, M.T.McClain, J.B.Harley, and J.A.James (2002).
Anti-U1A monoclonal antibodies recognize unique epitope targets of U1A which are involved in the binding of U1 RNA.
  J Mol Recognit, 15, 163-170.  
12434430 F.Pitici, D.L.Beveridge, and A.M.Baranger (2002).
Molecular dynamics simulation studies of induced fit and conformational capture in U1A-RNA binding: do molecular substates code for specificity?
  Biopolymers, 65, 424-435.  
12403777 I.D'Orso, and A.C.Frasch (2002).
TcUBP-1, an mRNA destabilizing factor from trypanosomes, homodimerizes and interacts with novel AU-rich element- and Poly(A)-binding proteins forming a ribonucleoprotein complex.
  J Biol Chem, 277, 50520-50528.  
12466552 J.B.Tuite, J.C.Shiels, and A.M.Baranger (2002).
Substitution of an essential adenine in the U1A-RNA complex with a non-polar isostere.
  Nucleic Acids Res, 30, 5269-5275.  
11788718 J.C.Shiels, J.B.Tuite, S.J.Nolan, and A.M.Baranger (2002).
Investigation of a conserved stacking interaction in target site recognition by the U1A protein.
  Nucleic Acids Res, 30, 550-558.  
12082087 P.S.Katsamba, M.Bayramyan, I.S.Haworth, D.G.Myszka, and I.A.Laird-Offringa (2002).
Complex role of the beta 2-beta 3 loop in the interaction of U1A with U1 hairpin II RNA.
  J Biol Chem, 277, 33267-33274.  
12202384 S.Kumar, and R.Nussinov (2002).
Relationship between ion pair geometries and electrostatic strengths in proteins.
  Biophys J, 83, 1595-1612.  
11141562 E.Jankowsky, C.H.Gross, S.Shuman, and A.M.Pyle (2001).
Active disruption of an RNA-protein interaction by a DExH/D RNA helicase.
  Science, 291, 121-125.  
11179892 J.M.Pérez-Cañadillas, and G.Varani (2001).
Recent advances in RNA-protein recognition.
  Curr Opin Struct Biol, 11, 53-58.  
11340660 S.Kumar, and R.Nussinov (2001).
Fluctuations in ion pairs and their stabilities in proteins.
  Proteins, 43, 433-454.  
11340059 W.Wang, O.Donini, C.M.Reyes, and P.A.Kollman (2001).
Biomolecular simulations: recent developments in force fields, simulations of enzyme catalysis, protein-ligand, protein-protein, and protein-nucleic acid noncovalent interactions.
  Annu Rev Biophys Biomol Struct, 30, 211-243.  
10852733 C.Clerte, and K.B.Hall (2000).
Spatial orientation and dynamics of the U1A proteins in the U1A-UTR complex.
  Biochemistry, 39, 7320-7329.  
10688667 J.M.Klein Gunnewiek, R.I.Hussein, Y.van Aarssen, D.Palacios, Jong, W.J.van Venrooij, and S.I.Gunderson (2000).
Fourteen residues of the U1 snRNP-specific U1A protein are required for homodimerization, cooperative RNA binding, and inhibition of polyadenylation.
  Mol Cell Biol, 20, 2209-2217.  
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
10675317 P.Nissen, M.Kjeldgaard, and J.Nyborg (2000).
Macromolecular mimicry.
  EMBO J, 19, 489-495.  
10024175 C.M.Reyes, and P.A.Kollman (1999).
Molecular dynamics studies of U1A-RNA complexes.
  RNA, 5, 235-244.  
10350468 D.E.Otzen, O.Kristensen, M.Proctor, and M.Oliveberg (1999).
Structural changes in the transition state of protein folding: alternative interpretations of curved chevron plots.
  Biochemistry, 38, 6499-6511.
PDB code: 1lou
10371034 E.Wahle, and U.Rüegsegger (1999).
3'-End processing of pre-mRNA in eukaryotes.
  FEMS Microbiol Rev, 23, 277-295.  
10588732 E.Welin Henriksson, M.Wahren-Herlenius, I.Lundberg, E.Mellquist, and I.Pettersson (1999).
Key residues revealed in a major conformational epitope of the U1-70K protein.
  Proc Natl Acad Sci U S A, 96, 14487-14492.  
  10548057 J.M.Jean, C.Clerte, and K.B.Hall (1999).
Global and local dynamics of the human U1A protein determined by tryptophan fluorescence.
  Protein Sci, 8, 2110-2120.  
10085088 P.Hanachi, J.W.Hershey, and H.P.Vornlocher (1999).
Characterization of the p33 subunit of eukaryotic translation initiation factor-3 from Saccharomyces cerevisiae.
  J Biol Chem, 274, 8546-8553.  
10611302 T.Ternström, U.Mayor, M.Akke, and M.Oliveberg (1999).
From snapshot to movie: phi analysis of protein folding transition states taken one step further.
  Proc Natl Acad Sci U S A, 96, 14854-14859.  
10026248 V.Gopalan, H.Kühne, R.Biswas, H.Li, G.W.Brudvig, and S.Altman (1999).
Mapping RNA-protein interactions in ribonuclease P from Escherichia coli using electron paramagnetic resonance spectroscopy.
  Biochemistry, 38, 1705-1714.  
10465742 Y.Tang, and L.Nilsson (1999).
Molecular dynamics simulations of the complex between human U1A protein and hairpin II of U1 small nuclear RNA and of free RNA in solution.
  Biophys J, 77, 1284-1305.  
9519296 A.M.Edwards, A.Bochkarev, and L.Frappier (1998).
Origin DNA-binding proteins.
  Curr Opin Struct Biol, 8, 49-53.  
9634694 B.Wang, D.N.Jones, B.P.Kaine, and M.A.Weiss (1998).
High-resolution structure of an archaeal zinc ribbon defines a general architectural motif in eukaryotic RNA polymerases.
  Structure, 6, 555-569.
PDB code: 1qyp
  9510334 D.L.Beck, W.T.Stump, and K.B.Hall (1998).
Defining the orientation of the human U1A RBD1 on its UTR by tethered-EDTA(Fe) cleavage.
  RNA, 4, 331-339.  
9646873 G.Varani, and K.Nagai (1998).
RNA recognition by RNP proteins during RNA processing.
  Annu Rev Biophys Biomol Struct, 27, 407-445.  
9562554 W.M.Clemons, C.Davies, S.W.White, and V.Ramakrishnan (1998).
Conformational variability of the N-terminal helix in the structure of ribosomal protein S15.
  Structure, 6, 429-438.
PDB code: 1a32
9204272 A.Ramos, C.C.Gubser, and G.Varani (1997).
Recent solution structures of RNA and its complexes with drugs, peptides and proteins.
  Curr Opin Struct Biol, 7, 317-323.  
9153306 A.Ramos, and G.Varani (1997).
Structure of the acceptor stem of Escherichia coli tRNA Ala: role of the G3.U70 base pair in synthetase recognition.
  Nucleic Acids Res, 25, 2083-2090.
PDB code: 1ikd
9312034 F.H.Allain, P.W.Howe, D.Neuhaus, and G.Varani (1997).
Structural basis of the RNA-binding specificity of human U1A protein.
  EMBO J, 16, 5764-5772.
PDB code: 1aud
9148924 G.Serin, G.Joseph, L.Ghisolfi, M.Bauzan, M.Erard, F.Amalric, and P.Bouvet (1997).
Two RNA-binding domains determine the RNA-binding specificity of nucleolin.
  J Biol Chem, 272, 13109-13116.  
9265619 J.Lu, and K.B.Hall (1997).
Tertiary structure of RBD2 and backbone dynamics of RBD1 and RBD2 of the human U1A protein determined by NMR spectroscopy.
  Biochemistry, 36, 10393-10405.
PDB code: 2u1a
9127942 J.Lu, and K.B.Hall (1997).
Thermal unfolding of the N-terminal RNA binding domain of the human U1A protein studied by differential scanning calorimetry.
  Biophys Chem, 64, 111-119.  
  9444478 P.A.Bullock (1997).
The initiation of simian virus 40 DNA replication in vitro.
  Crit Rev Biochem Mol Biol, 32, 503-568.  
9311984 P.Bouvet, C.Jain, J.G.Belasco, F.Amalric, and M.Erard (1997).
RNA recognition by the joint action of two nucleolin RNA-binding domains: genetic analysis and structural modeling.
  EMBO J, 16, 5235-5246.  
9164463 Y.Shamoo, U.Krueger, L.M.Rice, K.R.Williams, and T.A.Steitz (1997).
Crystal structure of the two RNA binding domains of human hnRNP A1 at 1.75 A resolution.
  Nat Struct Biol, 4, 215-222.
PDB code: 1ha1
8918800 F.Aboul-ela, J.Karn, and G.Varani (1996).
Structure of HIV-1 TAR RNA in the absence of ligands reveals a novel conformation of the trinucleotide bulge.
  Nucleic Acids Res, 24, 3974-3981.
PDB code: 1anr
8696973 K.Nagai (1996).
RNA-protein complexes.
  Curr Opin Struct Biol, 6, 53-61.  
8736559 L.Jovine, C.Oubridge, J.M.Avis, and K.Nagai (1996).
Two structurally different RNA molecules are bound by the spliceosomal protein U1A using the same recognition strategy.
  Structure, 4, 621-631.
PDB code: 3utr
8946857 X.Luo, D.G.Sanford, P.A.Bullock, and W.W.Bachovchin (1996).
Solution structure of the origin DNA-binding domain of SV40 T-antigen.
  Nat Struct Biol, 3, 1034-1039.
PDB codes: 1tbd 2tbd
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 code is shown on the right.