5h1k

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Crystal structure of WD40 repeat domains of Gemin5 in complex with 13-nt U4 snRNA fragment

Structural highlights

5h1k is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.9Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GEMI5_HUMAN The SMN complex plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Thereby, plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus. GEMIN5 acts as the snRNA-binding protein of the SMN complex.[1] [2] [3]

Publication Abstract from PubMed

Assembly of the spliceosomal small nuclear ribonucleoparticle (snRNP) core requires the participation of the multisubunit SMN (survival of motor neuron) complex, which contains SMN and several Gemin proteins. The SMN and Gemin2 subunits directly bind Sm proteins, and Gemin5 is required for snRNP biogenesis and has been implicated in snRNA recognition. The RNA sequence required for snRNP assembly includes the Sm site and an adjacent 3' stem-loop, but a precise understanding of Gemin5's RNA-binding specificity is lacking. Here we show that the N-terminal half of Gemin5, which is composed of two juxtaposed seven-bladed WD40 repeat domains, recognizes the Sm site. The tandem WD40 repeat domains are rigidly held together to form a contiguous RNA-binding surface. RNA-contacting residues are located mostly on loops between beta strands on the apical surface of the WD40 domains. Structural and biochemical analyses show that base-stacking interactions involving four aromatic residues and hydrogen bonding by a pair of arginines are crucial for specific recognition of the Sm sequence. We also show that an adenine immediately 5' to the Sm site is required for efficient binding and that Gemin5 can bind short RNA oligos in an alternative mode. Our results provide mechanistic understandings of Gemin5's snRNA-binding specificity as well as valuable insights into the molecular mechanism of RNA binding by WD40 repeat proteins in general.

Structural basis for snRNA recognition by the double-WD40 repeat domain of Gemin5.,Jin W, Wang Y, Liu CP, Yang N, Jin M, Cong Y, Wang M, Xu RM Genes Dev. 2016 Nov 1;30(21):2391-2403. Epub 2016 Nov 10. PMID:27881601[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
6 reviews cite this structure
Long Noncoding RNA in Cancer: Wiring Signaling Circuitry.
Lin et al. (2018)
5 more
24 other articles
No citations found

References

  1. ↑ Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G. Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins. J Biol Chem. 2002 Feb 15;277(7):5631-6. Epub 2001 Nov 19. PMID:11714716 doi:http://dx.doi.org/10.1074/jbc.M109448200
  2. ↑ Battle DJ, Lau CK, Wan L, Deng H, Lotti F, Dreyfuss G. The Gemin5 protein of the SMN complex identifies snRNAs. Mol Cell. 2006 Jul 21;23(2):273-9. PMID:16857593 doi:http://dx.doi.org/S1097-2765(06)00378-9
  3. ↑ Chari A, Golas MM, Klingenhager M, Neuenkirchen N, Sander B, Englbrecht C, Sickmann A, Stark H, Fischer U. An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs. Cell. 2008 Oct 31;135(3):497-509. doi: 10.1016/j.cell.2008.09.020. PMID:18984161 doi:http://dx.doi.org/10.1016/j.cell.2008.09.020
  4. ↑ Jin W, Wang Y, Liu CP, Yang N, Jin M, Cong Y, Wang M, Xu RM. Structural basis for snRNA recognition by the double-WD40 repeat domain of Gemin5. Genes Dev. 2016 Nov 1;30(21):2391-2403. Epub 2016 Nov 10. PMID:27881601 doi:http://dx.doi.org/10.1101/gad.291377.116

Contents


PDB ID 5h1k

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