7xur

From Proteopedia

The cryo-EM structure of human mini-SNAPc in complex with hU6-1 PSE

PDB ID 7xur

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Structural highlights

7xur is a 5 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.49Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SNPC4_HUMAN The disease is caused by variants affecting the gene represented in this entry.

Function

SNPC4_HUMAN Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box.^[1] ^[2]

Publication Abstract from PubMed

In eukaryotes, small nuclear RNAs (snRNAs) function in many fundamental cellular events such as precursor messenger RNA splicing, gene expression regulation, and ribosomal RNA processing. The snRNA activating protein complex (SNAPc) exclusively recognizes the proximal sequence element (PSE) at snRNA promoters and recruits RNA polymerase II or III to initiate transcription. In view that homozygous gene-knockout of SNAPc core subunits causes mouse embryonic lethality, functions of SNAPc are almost housekeeping. But so far, the structural insight into how SNAPc assembles and regulates snRNA transcription initiation remains unclear. Here we present the cryo-electron microscopy structure of the essential part of human SNAPc in complex with human U6-1 PSE at an overall resolution of 3.49 A. This structure reveals the three-dimensional features of three conserved subunits (N-terminal domain of SNAP190, SNAP50, and SNAP43) and explains how they are assembled into a stable mini-SNAPc in PSE-binding state with a "wrap-around" mode. We identify three important motifs of SNAP50 that are involved in both major groove and minor groove recognition of PSE, in coordination with the Myb domain of SNAP190. Our findings further elaborate human PSE sequence conservation and compatibility for SNAPc recognition, providing a clear framework of snRNA transcription initiation, especially the U6 system.

Structural basis of human SNAPc recognizing proximal sequence element of snRNA promoter.,Sun J, Li X, Hou X, Cao S, Cao W, Zhang Y, Song J, Wang M, Wang H, Yan X, Li Z, Roeder RG, Wang W Nat Commun. 2022 Nov 11;13(1):6871. doi: 10.1038/s41467-022-34639-1. PMID:36369505^[3]

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

References

↑ Hinkley CS, Hirsch HA, Gu L, LaMere B, Henry RW. The small nuclear RNA-activating protein 190 Myb DNA binding domain stimulates TATA box-binding protein-TATA box recognition. J Biol Chem. 2003 May 16;278(20):18649-57. Epub 2003 Mar 5. PMID:12621023 doi:http://dx.doi.org/10.1074/jbc.M204247200
↑ Wong MW, Henry RW, Ma B, Kobayashi R, Klages N, Matthias P, Strubin M, Hernandez N. The large subunit of basal transcription factor SNAPc is a Myb domain protein that interacts with Oct-1. Mol Cell Biol. 1998 Jan;18(1):368-77. PMID:9418884
↑ Sun J, Li X, Hou X, Cao S, Cao W, Zhang Y, Song J, Wang M, Wang H, Yan X, Li Z, Roeder RG, Wang W. Structural basis of human SNAPc recognizing proximal sequence element of snRNA promoter. Nat Commun. 2022 Nov 11;13(1):6871. doi: 10.1038/s41467-022-34639-1. PMID:36369505 doi:http://dx.doi.org/10.1038/s41467-022-34639-1