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PDBsum entry 1up1
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Nuclear protein
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PDB id
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1up1
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* Residue conservation analysis
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PDB id:
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Nuclear protein
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Title:
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Up1, the two RNA-recognition motif domain of hnrnp a1
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Structure:
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Heterogeneous nuclear ribonucleoprotein a1. Chain: a. Fragment: the two RNA-recognition motif domain, 1 - 196. Synonym: hnrnp a1, up1
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Source:
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Homo sapiens. Human. Organism_taxid: 9606
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Resolution:
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1.90Å
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R-factor:
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0.197
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R-free:
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0.254
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Authors:
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R.-M.Xu,L.Jokhan,X.Cheng,A.Mayeda,A.R.Krainer
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Key ref:
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R.M.Xu
et al.
(1997).
Crystal structure of human UP1, the domain of hnRNP A1 that contains two RNA-recognition motifs.
Structure,
5,
559-570.
PubMed id:
DOI:
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Date:
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12-Mar-97
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Release date:
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17-Sep-97
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PROCHECK
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Headers
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References
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P09651
(ROA1_HUMAN) -
Heterogeneous nuclear ribonucleoprotein A1 from Homo sapiens
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Seq:
Struc:
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372 a.a.
170 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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Structure
5:559-570
(1997)
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PubMed id:
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Crystal structure of human UP1, the domain of hnRNP A1 that contains two RNA-recognition motifs.
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R.M.Xu,
L.Jokhan,
X.Cheng,
A.Mayeda,
A.R.Krainer.
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ABSTRACT
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BACKGROUND: Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is one of the
most abundant core proteins of hnRNP complexes in metazoan nuclei. It behaves as
a global regulator of alternative pre-mRNA splicing by antagonizing the
activities of several serine/arginine-rich splicing factors (SR proteins),
resulting in the activation of distal alternative 5' splice sites and skipping
of optional exons. Purified hnRNP A1 has nucleic acid annealing activity. The
protein also shuttles continuously between the nucleus and the cytoplasm, a
process mediated by signals within its C-terminal glycine-rich domain. The
N-terminal region of human hnRNP A1, termed unwinding protein 1 (UP1), contains
two RNA-recognition motifs (RRMs), RRM1 and RRM2. Understanding the structural
elements by which hnRNP A1 interacts with RNA will have broad implications for
studies of RNA processing. RESULTS: The crystal structure of UP1 has been
determined to 1.9 A resolution. Each RRM independently adopts the characteristic
RRM fold, consisting of a four-stranded antiparallel beta-pleated sheet and two
alpha helices packed on one side of the beta sheet. The two RRMs are
antiparallel and held in close contact, mainly by two Arg-Asp ion pairs. As a
result, the two four-stranded beta sheets are brought together to form an
extended RNA-binding surface. A segment of the linker connecting the two RRMs is
flexible in the absence of bound RNA, but the general location of the linker
suggests that it can make direct contacts with RNA. Comparison with other RRM
structures indicates that a short 310 helix, found immediately N-terminal to the
first beta strand in RRM1, may interact with RNA directly. CONCLUSIONS: The RRM
is one of the most common and best characterized RNA-binding motifs. In certain
cases, one RRM is sufficient for sequence-specific and high affinity RNA
binding; but in other cases, synergy between several RRMs within a single
protein is required. This study shows how two RRMs are organized in a single
polypeptide. The two independently folded RRMs in UP1 are held together in a
fixed geometry, enabling the two RRMs to function as a single entity in binding
RNA, and so explaining the synergy between the RRMs. The UP1 structure also
suggests that residues which lie outside of the RRMs can make potentially
important interactions with RNA.
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Selected figure(s)
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Figure 1.
Figure 1. Overall folding of UP1. (a) Ribbon diagram of the
UP1 structure, viewed from the front (b-sheet side) of the
molecule. The conserved RNP-2 and RNP-1 submotifs are colored
cyan and purple, respectively. Red indicates the disordered
portion of the linker region; its placement is not based on
electron density, but was included for clarity. The N terminus
starts at Pro7, and the C terminus ends at Ser182. (b) Side view
of the overall folding of UP1. Diagrams were generated with the
Ribbons program [67].
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1997,
5,
559-570)
copyright 1997.
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Figure was
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.Jacobs,
and
U.Kück
(2011).
Function of chloroplast RNA-binding proteins.
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Cell Mol Life Sci,
68,
735-748.
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C.M.Maynard,
and
K.B.Hall
(2010).
Interactions between PTB RRMs induce slow motions and increase RNA binding affinity.
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J Mol Biol,
397,
260-277.
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G.Michlewski,
and
J.F.Cáceres
(2010).
Antagonistic role of hnRNP A1 and KSRP in the regulation of let-7a biogenesis.
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Nat Struct Mol Biol,
17,
1011-1018.
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H.L.Okunola,
and
A.R.Krainer
(2009).
Cooperative-binding and splicing-repressive properties of hnRNP A1.
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Mol Cell Biol,
29,
5620-5631.
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T.T.Zhao,
T.E.Graber,
L.E.Jordan,
M.Cloutier,
S.M.Lewis,
I.Goulet,
J.Côté,
and
M.Holcik
(2009).
hnRNP A1 regulates UV-induced NF-kappaB signalling through destabilization of cIAP1 mRNA.
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Cell Death Differ,
16,
244-252.
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G.Toba,
and
K.White
(2008).
The third RNA recognition motif of Drosophila ELAV protein has a role in multimerization.
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Nucleic Acids Res,
36,
1390-1399.
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T.Nagata,
Y.Takada,
A.Ono,
K.Nagata,
Y.Konishi,
T.Nukina,
M.Ono,
A.Matsugami,
A.Furukawa,
N.Fujimoto,
H.Fukuda,
H.Nakagama,
and
M.Katahira
(2008).
Elucidation of the mode of interaction in the UP1-telomerase RNA-telomeric DNA ternary complex which serves to recruit telomerase to telomeric DNA and to enhance the telomerase activity.
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Nucleic Acids Res,
36,
6816-6824.
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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.
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Proteomics,
8,
484-494.
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N.Satija,
and
S.K.Lal
(2007).
The molecular biology of SARS coronavirus.
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Ann N Y Acad Sci,
1102,
26-38.
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K.Oresic,
V.Noriega,
L.Andrews,
and
D.Tortorella
(2006).
A structural determinant of human cytomegalovirus US2 dictates the down-regulation of class I major histocompatibility molecules.
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J Biol Chem,
281,
19395-19406.
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C.Maris,
C.Dominguez,
and
F.H.Allain
(2005).
The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression.
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FEBS J,
272,
2118-2131.
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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.
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Nucleic Acids Res,
33,
486-496.
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C.Alfano,
D.Sanfelice,
J.Babon,
G.Kelly,
A.Jacks,
S.Curry,
and
M.R.Conte
(2004).
Structural analysis of cooperative RNA binding by the La motif and central RRM domain of human La protein.
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Nat Struct Mol Biol,
11,
323-329.
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PDB codes:
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C.G.Noble,
P.A.Walker,
L.J.Calder,
and
I.A.Taylor
(2004).
Rna14-Rna15 assembly mediates the RNA-binding capability of Saccharomyces cerevisiae cleavage factor IA.
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Nucleic Acids Res,
32,
3364-3375.
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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.
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Structure,
12,
1631-1643.
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PDB codes:
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D.L.Black
(2003).
Mechanisms of alternative pre-messenger RNA splicing.
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Annu Rev Biochem,
72,
291-336.
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J.C.Myers,
S.A.Moore,
and
Y.Shamoo
(2003).
Structure-based incorporation of 6-methyl-8-(2-deoxy-beta-ribofuranosyl)isoxanthopteridine into the human telomeric repeat DNA as a probe for UP1 binding and destabilization of G-tetrad structures.
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J Biol Chem,
278,
42300-42306.
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PDB codes:
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J.M.Pérez Cañadillas,
and
G.Varani
(2003).
Recognition of GU-rich polyadenylation regulatory elements by human CstF-64 protein.
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EMBO J,
22,
2821-2830.
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PDB code:
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M.M.Golas,
B.Sander,
C.L.Will,
R.Lührmann,
and
H.Stark
(2003).
Molecular architecture of the multiprotein splicing factor SF3b.
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Science,
300,
980-984.
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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.
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Nucleic Acids Res,
30,
1531-1538.
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PDB code:
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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.
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Mol Biol Cell,
13,
3683-3695.
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P.Weisman-Shomer,
E.Cohen,
and
M.Fry
(2002).
Distinct domains in the CArG-box binding factor A destabilize tetraplex forms of the fragile X expanded sequence d(CGG)n.
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Nucleic Acids Res,
30,
3672-3681.
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Z.J.Lorković,
and
A.Barta
(2002).
Genome analysis: RNA recognition motif (RRM) and K homology (KH) domain RNA-binding proteins from the flowering plant Arabidopsis thaliana.
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Nucleic Acids Res,
30,
623-635.
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D.C.Hay,
G.D.Kemp,
C.Dargemont,
and
R.T.Hay
(2001).
Interaction between hnRNPA1 and IkappaBalpha is required for maximal activation of NF-kappaB-dependent transcription.
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Mol Cell Biol,
21,
3482-3490.
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C.L.Fong,
A.Lentz,
and
S.P.Mayfield
(2000).
Disulfide bond formation between RNA binding domains is used to regulate mRNA binding activity of the chloroplast poly(A)-binding protein.
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J Biol Chem,
275,
8275-8278.
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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.
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EMBO J,
19,
3132-3141.
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PDB code:
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P.C.Zuzarte,
I.K.Farrance,
P.C.Simpson,
and
A.G.Wildeman
(2000).
Tumor cell splice variants of the transcription factor TEF-1 induced by SV40 T-antigen transformation.
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Biochim Biophys Acta,
1517,
82-90.
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V.Markovtsov,
J.M.Nikolic,
J.A.Goldman,
C.W.Turck,
M.Y.Chou,
and
D.L.Black
(2000).
Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein.
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Mol Cell Biol,
20,
7463-7479.
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W.van Der Houven Van Oordt,
K.Newton,
G.R.Screaton,
and
J.F.Cáceres
(2000).
Role of SR protein modular domains in alternative splicing specificity in vivo.
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Nucleic Acids Res,
28,
4822-4831.
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J.Ding,
M.K.Hayashi,
Y.Zhang,
L.Manche,
A.R.Krainer,
and
R.M.Xu
(1999).
Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA.
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Genes Dev,
13,
1102-1115.
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PDB code:
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J.J.Smith,
K.P.Rücknagel,
A.Schierhorn,
J.Tang,
A.Nemeth,
M.Linder,
H.R.Herschman,
and
E.Wahle
(1999).
Unusual sites of arginine methylation in Poly(A)-binding protein II and in vitro methylation by protein arginine methyltransferases PRMT1 and PRMT3.
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J Biol Chem,
274,
13229-13234.
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M.Caputi,
A.Mayeda,
A.R.Krainer,
and
A.M.Zahler
(1999).
hnRNP A/B proteins are required for inhibition of HIV-1 pre-mRNA splicing.
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EMBO J,
18,
4060-4067.
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S.M.Crowder,
R.Kanaar,
D.C.Rio,
and
T.Alber
(1999).
Absence of interdomain contacts in the crystal structure of the RNA recognition motifs of Sex-lethal.
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Proc Natl Acad Sci U S A,
96,
4892-4897.
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PDB code:
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S.W.Chi,
Y.Muto,
M.Inoue,
I.Kim,
H.Sakamoto,
Y.Shimura,
S.Yokoyama,
B.S.Choi,
and
H.Kim
(1999).
Chemical shift perturbation studies of the interactions of the second RNA-binding domain of the Drosophila sex-lethal protein with the transformer pre-mRNA polyuridine tract and 3' splice-site sequences.
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Eur J Biochem,
260,
649-660.
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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)).
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EMBO J,
18,
4523-4534.
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PDB codes:
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Y.Zhao,
D.Jeruzalmi,
I.Moarefi,
L.Leighton,
R.Lasken,
and
J.Kuriyan
(1999).
Crystal structure of an archaebacterial DNA polymerase.
|
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Structure,
7,
1189-1199.
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PDB codes:
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A.M.Edwards,
A.Bochkarev,
and
L.Frappier
(1998).
Origin DNA-binding proteins.
|
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Curr Opin Struct Biol,
8,
49-53.
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A.Mayeda,
S.H.Munroe,
R.M.Xu,
and
A.R.Krainer
(1998).
Distinct functions of the closely related tandem RNA-recognition motifs of hnRNP A1.
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RNA,
4,
1111-1123.
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C.F.Kennedy,
A.Krämer,
and
S.M.Berget
(1998).
A role for SRp54 during intron bridging of small introns with pyrimidine tracts upstream of the branch point.
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Mol Cell Biol,
18,
5425-5434.
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G.Varani,
and
K.Nagai
(1998).
RNA recognition by RNP proteins during RNA processing.
|
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Annu Rev Biophys Biomol Struct,
27,
407-445.
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J.P.Staley,
and
C.Guthrie
(1998).
Mechanical devices of the spliceosome: motors, clocks, springs, and things.
|
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Cell,
92,
315-326.
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K.Zu,
M.L.Sikes,
and
A.L.Beyer
(1998).
Separable roles in vivo for the two RNA binding domains of Drosophila A1-hnRNP homolog.
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RNA,
4,
1585-1598.
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M.Samuels,
G.Deshpande,
and
P.Schedl
(1998).
Activities of the Sex-lethal protein in RNA binding and protein:protein interactions.
|
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Nucleic Acids Res,
26,
2625-2637.
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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.
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EMBO J,
16,
5235-5246.
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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.
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Links
