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Contents |
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76 a.a.*
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64 a.a.*
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77 a.a.*
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88 a.a.*
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76 a.a.*
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75 a.a.*
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73 a.a.*
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120 a.a.*
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57 a.a.*
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70 a.a.*
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89 a.a.*
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54 a.a.*
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* Residue conservation analysis
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* C-alpha coords only
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PDB id:
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| Name: |
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Splicing
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Title:
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Crystal structure of human spliceosomal u1 snrnp
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Structure:
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U1 snrna. Chain: v, v, w, x. Fragment: nucleotides 57-82 absent, replaced with kissing l engineered: yes. Mutation: yes. Small nuclear ribonucleoprotein sm d3. Chain: d, s, t, u. Synonym: snrnp core protein d3, sm-d3. Engineered: yes.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: rnu1a. Other_details: in vitro transcribed with t7 RNA polymerase. Gene: snrpd3. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: coexpressed with sm b, entity 2.
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Resolution:
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5.49Å
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R-factor:
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not given
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Authors:
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D.A.Pomeranz Krummel,C.Oubridge,A.K.Leung,J.Li,K.Nagai
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Key ref:
|
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D.A.Pomeranz Krummel
et al.
(2009).
Crystal structure of human spliceosomal U1 snRNP at 5.5 A resolution.
Nature,
458,
475-480.
PubMed id:
DOI:
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Date:
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21-Apr-08
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Release date:
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24-Mar-09
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P62318
(SMD3_HUMAN) -
Small nuclear ribonucleoprotein Sm D3
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Seq: Struc:
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126 a.a.
76 a.a.*
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P14678
(RSMB_HUMAN) -
Small nuclear ribonucleoprotein-associated proteins B and B'
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Seq: Struc:
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240 a.a.
64 a.a.
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P62314
(SMD1_HUMAN) -
Small nuclear ribonucleoprotein Sm D1
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Seq: Struc:
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119 a.a.
77 a.a.
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P62316
(SMD2_HUMAN) -
Small nuclear ribonucleoprotein Sm D2
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Seq: Struc:
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118 a.a.
88 a.a.
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P62306
(RUXF_HUMAN) -
Small nuclear ribonucleoprotein F
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Seq: Struc:
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86 a.a.
76 a.a.
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P62304
(RUXE_HUMAN) -
Small nuclear ribonucleoprotein E
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Seq: Struc:
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92 a.a.
75 a.a.
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P62308
(RUXG_HUMAN) -
Small nuclear ribonucleoprotein G
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Seq: Struc:
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76 a.a.
73 a.a.
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P08621
(RU17_HUMAN) -
U1 small nuclear ribonucleoprotein 70 kDa
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Seq: Struc:
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437 a.a.
120 a.a.
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P09234
(RU1C_HUMAN) -
U1 small nuclear ribonucleoprotein C
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Seq: Struc:
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159 a.a.
57 a.a.*
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P62306
(RUXF_HUMAN) -
Small nuclear ribonucleoprotein F
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Seq: Struc:
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86 a.a.
70 a.a.
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Gene Ontology (GO) functional annotation
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Cellular component
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catalytic step 2 spliceosome
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10 terms
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Biological process
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gene expression
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12 terms
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Biochemical function
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histone pre-mRNA DCP binding
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7 terms
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DOI no:
|
Nature
458:475-480
(2009)
|
|
PubMed id:
|
|
|
|
|
| |
|
Crystal structure of human spliceosomal U1 snRNP at 5.5 A resolution.
|
|
D.A.Pomeranz Krummel,
C.Oubridge,
A.K.Leung,
J.Li,
K.Nagai.
|
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|
| |
ABSTRACT
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| |
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Human spliceosomal U1 small nuclear ribonucleoprotein particles (snRNPs), which
consist of U1 small nuclear RNA and ten proteins, recognize the 5' splice site
within precursor messenger RNAs and initiate the assembly of the spliceosome for
intron excision. An electron density map of the functional core of U1 snRNP at
5.5 A resolution has enabled us to build the RNA and, in conjunction with
site-specific labelling of individual proteins, to place the seven Sm proteins,
U1-C and U1-70K into the map. Here we present the detailed structure of a
spliceosomal snRNP, revealing a hierarchical network of intricate interactions
between subunits. A striking feature is the amino (N)-terminal polypeptide of
U1-70K, which extends over a distance of 180 A from its RNA binding domain,
wraps around the core domain consisting of the seven Sm proteins and finally
contacts U1-C, which is crucial for 5'-splice-site recognition. The structure of
U1 snRNP provides insights into U1 snRNP assembly and suggests a possible
mechanism of 5'-splice-site recognition.
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Selected figure(s)
|
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| |
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|
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Figure 2.
Figure 2: Structure of the U1 snRNP core domain. a, The Sm
proteins and the experimental electron density map (contoured at
1 ).
Cartwheel-shaped density in the central hole of the U1 snRNP
core domain is attributed to the seven Sm site nucleotides. b,
The N terminus of Sm-D2 supporting helix H. The extended
polypeptide of U1-70K interacts with Sm-D2. SeMet anomalous
peaks from natural (Met 67; red) and engineered Met residues
(I41M, E49M and E61M; orange) of U1-70K and of Sm-D2 (Met 11;
cyan). The asterisk indicates a 'bump' due to Phe 24 of Sm-D2.
c, The N terminus of Sm-B interacting with the phosphate
backbone of SL2. Navy blue spheres, anomalous peaks from
SeMet-labelled Sm-B.
|
 |
Figure 5.
Figure 5: Model of the complete human U1 snRNP. a, Overview
of a model of the complete U1 snRNP. Truncated SL2 was extended
with A-form RNA and the crystal structure of the U1A–RNA
complex^19 was appended to the extended helix. The internal loop
of SL2, consisting of four consecutive non-Watson–Crick base
pairs (red), is in a position to interact with Sm-B and Sm-D1.
b, Two views of the complete U1 snRNP model approximately
45° apart, with surface representation superimposed. Closely
matching images are found in the gallery of negatively stained
images of U1 snRNP reported previously^23, ^24.
|
 |
|
|
|
| |
The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
Nature
(2009,
458,
475-480)
copyright 2009.
|
|
| |
Figures were
selected
by the author.
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Literature references that cite this PDB file's key reference
|
|
 |
| |
PubMed id
|
 |
Reference
|
 |
|
|
|
 |
A.K.Leung,
K.Nagai,
and
J.Li
(2011).
Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis.
|
| |
Nature, 473,
536-539.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
B.Pradet-Balade,
C.Girard,
S.Boulon,
C.Paul,
K.Azzag,
R.Bordonné,
E.Bertrand,
and
C.Verheggen
(2011).
CRM1 controls the composition of nucleoplasmic pre-snoRNA complexes to licence them for nucleolar transport.
|
| |
EMBO J, 30,
2205-2218.
|
 |
|
|
|
|
 |
S.Sharma,
C.Maris,
F.H.Allain,
and
D.L.Black
(2011).
U1 snRNA directly interacts with polypyrimidine tract-binding protein during splicing repression.
|
| |
Mol Cell, 41,
579-588.
|
 |
|
|
|
|
 |
A.Chari,
and
U.Fischer
(2010).
Cellular strategies for the assembly of molecular machines.
|
| |
Trends Biochem Sci, 35,
676-683.
|
 |
|
|
|
|
 |
A.R.Ferré-D'Amaré
(2010).
Use of the spliceosomal protein U1A to facilitate crystallization and structure determination of complex RNAs.
|
| |
Methods, 52,
159-167.
|
 |
|
|
|
|
 |
C.J.David,
M.Chen,
M.Assanah,
P.Canoll,
and
J.L.Manley
(2010).
HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer.
|
| |
Nature, 463,
364-368.
|
 |
|
|
|
|
 |
E.Kühn-Hölsken,
C.Lenz,
A.Dickmanns,
H.H.Hsiao,
F.M.Richter,
B.Kastner,
R.Ficner,
and
H.Urlaub
(2010).
Mapping the binding site of snurportin 1 on native U1 snRNP by cross-linking and mass spectrometry.
|
| |
Nucleic Acids Res, 38,
5581-5593.
|
 |
|
|
|
|
 |
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:
|
 |
|
|
|
|
|
 |
K.Ohe,
and
A.Mayeda
(2010).
HMGA1a trapping of U1 snRNP at an authentic 5' splice site induces aberrant exon skipping in sporadic Alzheimer's disease.
|
| |
Mol Cell Biol, 30,
2220-2228.
|
 |
|
|
|
|
 |
M.Bragulat,
M.Meyer,
S.Macías,
M.Camats,
M.Labrador,
and
J.Vilardell
(2010).
RPL30 regulation of splicing reveals distinct roles for Cbp80 in U1 and U2 snRNP cotranscriptional recruitment.
|
| |
RNA, 16,
2033-2041.
|
 |
|
|
|
|
 |
M.D.Daugherty,
D.S.Booth,
B.Jayaraman,
Y.Cheng,
and
A.D.Frankel
(2010).
HIV Rev response element (RRE) directs assembly of the Rev homooligomer into discrete asymmetric complexes.
|
| |
Proc Natl Acad Sci U S A, 107,
12481-12486.
|
 |
|
|
|
|
 |
M.Lech,
V.Skuginna,
O.P.Kulkarni,
J.Gong,
T.Wei,
R.W.Stark,
C.Garlanda,
A.Mantovani,
and
H.J.Anders
(2010).
Lack of SIGIRR/TIR8 aggravates hydrocarbon oil-induced lupus nephritis.
|
| |
J Pathol, 220,
596-607.
|
 |
|
|
|
|
 |
M.M.Golas,
B.Sander,
S.Bessonov,
M.Grote,
E.Wolf,
B.Kastner,
H.Stark,
and
R.Lührmann
(2010).
3D cryo-EM structure of an active step I spliceosome and localization of its catalytic core.
|
| |
Mol Cell, 40,
927-938.
|
 |
|
|
|
|
 |
M.R.Alexander,
A.K.Wheatley,
R.J.Center,
and
D.F.Purcell
(2010).
Efficient transcription through an intron requires the binding of an Sm-type U1 snRNP with intact stem loop II to the splice donor.
|
| |
Nucleic Acids Res, 38,
3041-3053.
|
 |
|
|
|
|
 |
M.W.Górna,
Z.Pietras,
Y.C.Tsai,
A.J.Callaghan,
H.Hernández,
C.V.Robinson,
and
B.F.Luisi
(2010).
The regulatory protein RraA modulates RNA-binding and helicase activities of the E. coli RNA degradosome.
|
| |
RNA, 16,
553-562.
|
 |
|
|
|
|
 |
M.Zhou,
and
C.V.Robinson
(2010).
When proteomics meets structural biology.
|
| |
Trends Biochem Sci, 35,
522-529.
|
 |
|
|
|
|
 |
N.H.Kattah,
M.G.Kattah,
and
P.J.Utz
(2010).
The U1-snRNP complex: structural properties relating to autoimmune pathogenesis in rheumatic diseases.
|
| |
Immunol Rev, 233,
126-145.
|
 |
|
|
|
|
 |
S.Valadkhan,
and
Y.Jaladat
(2010).
The spliceosomal proteome: at the heart of the largest cellular ribonucleoprotein machine.
|
| |
Proteomics, 10,
4128-4141.
|
 |
|
|
|
|
 |
A.Bhattacharya
(2009).
Protein structures: Structures of desire.
|
| |
Nature, 459,
24-27.
|
 |
|
|
|
|
 |
C.C.Query
(2009).
Structural biology: Spliceosome subunit revealed.
|
| |
Nature, 458,
418-419.
|
 |
|
|
|
|
 |
C.Oubridge,
D.A.Krummel,
A.K.Leung,
J.Li,
and
K.Nagai
(2009).
Interpreting a low resolution map of human U1 snRNP using anomalous scatterers.
|
| |
Structure, 17,
930-938.
|
 |
|
|
|
|
 |
H.Hernández,
O.V.Makarova,
E.M.Makarov,
N.Morgner,
Y.Muto,
D.P.Krummel,
and
C.V.Robinson
(2009).
Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP.
|
| |
PLoS One, 4,
e7202.
|
 |
|
|
|
|
 |
J.F.Kugel,
and
J.A.Goodrich
(2009).
In new company: U1 snRNA associates with TAF15.
|
| |
EMBO Rep, 10,
454-456.
|
 |
|
|
|
|
 |
R.Hage,
L.Tung,
H.Du,
L.Stands,
M.Rosbash,
and
T.H.Chang
(2009).
A targeted bypass screen identifies Ynl187p, Prp42p, Snu71p, and Cbp80p for stable U1 snRNP/Pre-mRNA interaction.
|
| |
Mol Cell Biol, 29,
3941-3952.
|
 |
|
|
|
|
 |
T.M.Link,
P.Valentin-Hansen,
and
R.G.Brennan
(2009).
Structure of Escherichia coli Hfq bound to polyriboadenylate RNA.
|
| |
Proc Natl Acad Sci U S A, 106,
19292-19297.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
Y.Nie,
C.Viola,
C.Bieniossek,
S.Trowitzsch,
L.S.Vijay-Achandran,
M.Chaillet,
F.Garzoni,
and
I.Berger
(2009).
Getting a grip on complexes.
|
| |
Curr Genomics, 10,
558-572.
|
 |
|
 |
 |
|
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.
|
| |