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PDBsum entry 4f93

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protein ligands metals links
Hydrolase PDB id
4f93
Jmol PyMol
Contents
Protein chain
1723 a.a.
Ligands
ADP
ATP
SAN
Metals
_MG
Waters ×51
PDB id:
4f93
Name: Hydrolase
Title: Brr2 helicase region s1087l, mg-atp
Structure: U5 small nuclear ribonucleoprotein 200 kda helica chain: b. Fragment: brr2 helicase region. Synonym: activating signal cointegrator 1 complex subunit 3 brr2 homolog, u5 snrnp-specific 200 kda protein, u5-200kd. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: snrnp200, ascc3l1, helic2, kiaa0788. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108
Resolution:
2.92Å     R-factor:   0.200     R-free:   0.248
Authors: K.F.Santos,S.M.Jovin,G.Weber,V.Pena,R.Luehrmann,M.C.Wahl
Key ref: 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: 23045696 DOI: 10.1073/pnas.1208098109
Date:
18-May-12     Release date:   17-Oct-12    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O75643  (U520_HUMAN) -  U5 small nuclear ribonucleoprotein 200 kDa helicase
Seq:
Struc:
 
Seq:
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Seq:
Struc:
 
Seq:
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Seq:
Struc:
2136 a.a.
1723 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

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

 

 
DOI no: 10.1073/pnas.1208098109 Proc Natl Acad Sci U S A 109:17418-17423 (2012)
PubMed id: 23045696  
 
 
Structural basis for functional cooperation between tandem helicase cassettes in Brr2-mediated remodeling of the spliceosome.
K.F.Santos, S.M.Jovin, G.Weber, V.Pena, R.Lührmann, M.C.Wahl.
 
  ABSTRACT  
 
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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