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PDBsum entry 4f91
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PDB id:
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Hydrolase
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Title:
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Brr2 helicase region
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Structure:
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U5 small nuclear ribonucleoprotein 200 kda helicase. Chain: b. Fragment: brr2 helicase region. Synonym: activating signal cointegrator 1 complex subunit 3-like 1, brr2 homolog, u5 snrnp-specific 200 kda protein, u5-200kd. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: snrnp200, ascc3l1, helic2, kiaa0788. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108
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Resolution:
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2.70Å
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R-factor:
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0.226
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R-free:
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0.272
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Authors:
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K.F.Santos,S.M.Jovin,G.Weber,V.Pena,R.Luehrmann,M.C.Wahl
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Key ref:
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K.F.Santos
et al.
(2012).
Structural basis for functional cooperation between tandem helicase cassettes in Brr2-mediated remodeling of the spliceosome.
Proc Natl Acad Sci U S A,
109,
17418-17423.
PubMed id:
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Date:
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18-May-12
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Release date:
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17-Oct-12
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PROCHECK
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Headers
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References
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O75643
(U520_HUMAN) -
U5 small nuclear ribonucleoprotein 200 kDa helicase from Homo sapiens
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Seq:
Struc:
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2136 a.a.
1724 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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Enzyme class:
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E.C.3.6.4.13
- Rna helicase.
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Reaction:
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ATP + H2O = ADP + phosphate + H+
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ATP
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+
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H2O
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=
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ADP
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+
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phosphate
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Proc Natl Acad Sci U S A
109:17418-17423
(2012)
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PubMed id:
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Structural basis for functional cooperation between tandem helicase cassettes in Brr2-mediated remodeling of the spliceosome.
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K.F.Santos,
S.M.Jovin,
G.Weber,
V.Pena,
R.Lührmann,
M.C.Wahl.
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ABSTRACT
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Assembly of a spliceosome, catalyzing precursor-messenger RNA splicing, involves
multiple RNA-protein remodeling steps, driven by eight conserved DEXD/H-box RNA
helicases. The 250-kDa Brr2 enzyme, which is essential for U4/U6 di-small
nuclear ribonucleoprotein disruption during spliceosome catalytic activation and
for spliceosome disassembly, is the only member of this group that is
permanently associated with the spliceosome, thus requiring its faithful
regulation. At the same time, Brr2 represents a unique subclass of superfamily 2
nucleic acid helicases, containing tandem helicase cassettes. Presently, the
mechanistic and regulatory consequences of this unconventional architecture are
unknown. Here we show that in human Brr2, two ring-like helicase cassettes
intimately interact and functionally cooperate and how retinitis
pigmentosa-linked Brr2 mutations interfere with the enzyme's function. Only the
N-terminal cassette harbors ATPase and helicase activities in isolation.
Comparison with other helicases and mutational analyses show how it threads
single-stranded RNA, and structural features suggest how it can load onto an
internal region of U4/U6 di-snRNA. Although the C-terminal cassette does not
seem to engage RNA in the same fashion, it binds ATP and strongly stimulates the
N-terminal helicase. Mutations at the cassette interface, in an intercassette
linker or in the C-terminal ATP pocket, affect this cross-talk in diverse ways.
Together, our results reveal the structural and functional interplay between two
helicase cassettes in a tandem superfamily 2 enzyme and point to several sites
through which Brr2 activity may be regulated.
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Links
