3jcr | pdb_00003jcr

3D Structure determination of the human U5.U4/U6 tri-snRNP complex

spinqualitylabelsall models 3jcr, resolution 7.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3jcr is a 36 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Activity: RNA helicase, with EC number 3.6.4.13 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Disease [U5S1_HUMAN] Mandibulofacial dysostosis-microcephaly syndrome. The disease is caused by mutations affecting the gene represented in this entry. [PRPF3_HUMAN] Defects in PRPF3 are the cause of retinitis pigmentosa type 18 (RP18) [MIM:601414]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP18 inheritance is autosomal dominant. [PRP6_HUMAN] Retinitis pigmentosa. The disease may be caused by mutations affecting the gene represented in this entry. Cells from RP60 patients show intron retention for pre-mRNA bearing specific splicing signals. [U520_HUMAN] Retinitis pigmentosa. Retinitis pigmentosa 33 (RP33) [MIM:610359]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. Note=The disease is caused by mutations affecting the gene represented in this entry. [PRP31_HUMAN] Defects in PRPF31 are the cause of retinitis pigmentosa type 11 (RP11) [MIM:600138]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP11 inheritance is autosomal dominant. [PRP8_HUMAN] Defects in PRPF8 are the cause of retinitis pigmentosa type 13 (RP13) [MIM:600059]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP13 inheritance is autosomal dominant. [:] Function [SMD3_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Binds to the downstream cleavage product (DCP) of histone pre-mRNA in a U7 snRNP dependent manner. [LSM7_HUMAN] Binds specifically to the 3'-terminal U-tract of U6 snRNA and is probably a component of the spliceosome. [U5S1_HUMAN] Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex required for pre-mRNA splicing. Binds GTP. [SNUT2_HUMAN] Plays a role in pre-mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the spliceosome. Regulates AURKB mRNA levels, and thereby plays a role in cytokinesis and in the spindle checkpoint. Does not have ubiquitin-specific peptidase activity, but could be a competitor of ubiquitin C-terminal hydrolases (UCHs). [SNR40_HUMAN] Component of the U5 small nuclear ribonucleoprotein (snRNP) complex. The U5 snRNP is part of the spliceosome, a multiprotein complex that catalyzes the removal of introns from pre-messenger RNAs. [LSM5_HUMAN] Plays a role in U6 snRNP assembly and function. Binds to the 3' end of U6 snRNA, thereby facilitating formation of the spliceosomal U4/U6 duplex formation in vitro. [PRPF3_HUMAN] Participates in pre-mRNA splicing. May play a role in the assembly of the U4/U5/U6 tri-snRNP complex. [PRP6_HUMAN] Involved in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex, one of the building blocks of the spliceosome. Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but does not affect estrogen-induced transactivation. [LSM4_HUMAN] Binds specifically to the 3'-terminal U-tract of U6 snRNA. [RUXF_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. [LSM6_HUMAN] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner, facilitating the efficient association of RNA processing factors with their substrates. Component of the cytoplasmic LSM1-LSM7 complex, which is thought to be involved in mRNA degradation by activating the decapping step in the 5'-to-3' mRNA decay pathway. Component of the nuclear LSM2-LSM8 complex, which is involved in splicing of nuclear mRNAs. LSM2-LSM8 associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 di-snRNP, spliceosomal U4/U6.U5 tri-snRNP, and free U6 snRNP). It binds directly to the 3'-terminal U-tract of U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. LSM2-LSM8 probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping, and in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA (By similarity). [DDX23_HUMAN] Involved in pre-mRNA splicing and its phosphorylated form (by SRPK2) is required for spliceosomal B complex formation. [NH2L1_HUMAN] Binds to the 5'-stem-loop of U4 snRNA and may play a role in the late stage of spliceosome assembly. The protein undergoes a conformational change upon RNA-binding. [U520_HUMAN] RNA helicase that plays an essential role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes. Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome. [SMD1_HUMAN] May act as a charged protein scaffold to promote snRNP assembly or strengthen snRNP-snRNP interactions through nonspecific electrostatic contacts with RNA. [RUXE_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. [RUXG_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. [LSM8_HUMAN] Binds specifically to the 3'-terminal U-tract of U6 snRNA and is probably a component of the spliceosome. [LSM2_HUMAN] Binds specifically to the 3'-terminal U-tract of U6 snRNA. May be involved in pre-mRNA splicing. [RSMB_HUMAN] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. May have a functional role in the pre-mRNA splicing or in snRNP structure. Binds to the downstream cleavage product (DCP) of histone pre-mRNA in a U7 snRNP dependent manner (By similarity). [TXN4A_HUMAN] Essential role in pre-mRNA splicing. [PRP31_HUMAN] Involved in pre-mRNA splicing. Required for U4/U6.U5 tri-snRNP formation. [SMD2_HUMAN] Required for pre-mRNA splicing. Required for snRNP biogenesis (By similarity). [LSM3_HUMAN] Binds specifically to the 3'-terminal U-tract of U6 snRNA. [PRP8_HUMAN] Central component of the spliceosome, which may play a role in aligning the pre-mRNA 5'- and 3'-exons for ligation. Interacts with U5 snRNA, and with pre-mRNA 5'-splice sites in B spliceosomes and 3'-splice sites in C spliceosomes. Publication Abstract from PubMed The U4/U6.U5 triple small nuclear ribonucleoprotein (tri-snRNP) is a major spliceosome building block. Here we describe a 7 A 3D structure of the 1.8 MDa human tri-snRNP obtained by single-particle electron cryomicroscopy. We fit all known high-resolution structures of tri-snRNP components into the EM density map and validated them by protein crosslinking. Our model reveals how the spatial organization of Brr2 RNA helicase prevents pre-mature U4/U6 RNA unwinding in isolated human tri-snRNPs and how the Sad1 protein likely tethers Brr2 to its pre-activation position. Comparison of our model with cryo-EM 3D structures of the S. cerevisiae tri-snRNP and S. pombe spliceosome indicates that Brr2 undergoes a dramatic conformational change during spliceosome activation, and that Prp8 is also rearranged to accommodate the spliceosome's catalytic RNA network. Molecular architecture of the human U4/U6.U5 tri-snRNP.,Agafonov DE, Kastner B, Dybkov O, Hofele RV, Liu WT, Urlaub H, Luhrmann R, Stark H Science. 2016 Feb 18. pii: aad2085. PMID:26912367 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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