6lax

From Proteopedia

the mutant SAM-VI riboswitch (U6C) bound to SAM

PDB ID 6lax

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Structural highlights

6lax is a 5 chain structure with sequence from Bifidobacterium angulatum and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SNRPA_HUMAN Binds stem loop II of U1 snRNA. It is the first snRNP to interact with pre-mRNA. This interaction is required for the subsequent binding of U2 snRNP and the U4/U6/U5 tri-snRNP. In a snRNP-free form (SF-A) may be involved in coupled pre-mRNA splicing and polyadenylation process. Binds preferentially to the 5'-UGCAC-3' motif in vitro.^[1]

Publication Abstract from PubMed

Riboswitches are metabolite-sensing, conserved domains located in non-coding regions of mRNA that are central to regulation of gene expression. Here we report the first three-dimensional structure of the recently discovered S-adenosyl-L-methionine responsive SAM-VI riboswitch. SAM-VI adopts a unique fold and ligand pocket that are distinct from all other known SAM riboswitch classes. The ligand binds to the junctional region with its adenine tightly intercalated and Hoogsteen base-paired. Furthermore, we reveal the ligand discrimination mode of SAM-VI by additional X-ray structures of this riboswitch bound to S-adenosyl-L-homocysteine and a synthetic ligand mimic, in combination with isothermal titration calorimetry and fluorescence spectroscopy to explore binding thermodynamics and kinetics. The structure is further evaluated by analysis of ligand binding to SAM-VI mutants. It thus provides a thorough basis for developing synthetic SAM cofactors for applications in chemical and synthetic RNA biology.

SAM-VI riboswitch structure and signature for ligand discrimination.,Sun A, Gasser C, Li F, Chen H, Mair S, Krasheninina O, Micura R, Ren A Nat Commun. 2019 Dec 16;10(1):5728. doi: 10.1038/s41467-019-13600-9. PMID:31844059^[2]

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

References

↑ Lutz CS, Cooke C, O'Connor JP, Kobayashi R, Alwine JC. The snRNP-free U1A (SF-A) complex(es): identification of the largest subunit as PSF, the polypyrimidine-tract binding protein-associated splicing factor. RNA. 1998 Dec;4(12):1493-9. PMID:9848648
↑ Sun A, Gasser C, Li F, Chen H, Mair S, Krasheninina O, Micura R, Ren A. SAM-VI riboswitch structure and signature for ligand discrimination. Nat Commun. 2019 Dec 16;10(1):5728. doi: 10.1038/s41467-019-13600-9. PMID:31844059 doi:http://dx.doi.org/10.1038/s41467-019-13600-9