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4J7N

Crystal structure of mouse DXO in complex with M7GPPPG cap

Summary for 4J7N
Entry DOI10.2210/pdb4j7n/pdb
Related3FQI 3FQJ 4J7L 4J7M
DescriptorProtein Dom3Z, 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE-5'-GUANOSINE, 9-METHYLGUANINE, ... (5 entities in total)
Functional Keywordsdecapping, 5'-3' exoribonuclease, hydrolase
Biological sourceMus musculus (mouse)
Cellular locationNucleus (By similarity): O70348
Total number of polymer chains1
Total formula weight45028.70
Authors
Kilic, T.,Chang, J.H.,Tong, L. (deposition date: 2013-02-13, release date: 2013-03-27, Last modification date: 2024-02-28)
Primary citationJiao, X.,Chang, J.H.,Kilic, T.,Tong, L.,Kiledjian, M.
A mammalian pre-mRNA 5' end capping quality control mechanism and an unexpected link of capping to pre-mRNA processing.
Mol.Cell, 50:104-115, 2013
Cited by
PubMed Abstract: Recently, we reported that two homologous yeast proteins, Rai1 and Dxo1, function in a quality control mechanism to clear cells of incompletely 5' end-capped messenger RNAs (mRNAs). Here, we report that their mammalian homolog, Dom3Z (referred to as DXO), possesses pyrophosphohydrolase, decapping, and 5'-to-3' exoribonuclease activities. Surprisingly, we found that DXO preferentially degrades defectively capped pre-mRNAs in cells. Additional studies show that incompletely capped pre-mRNAs are inefficiently spliced at all introns, a fact that contrasts with current understanding, and are also poorly cleaved for polyadenylation. Crystal structures of DXO in complex with substrate mimic and products at a resolution of up to 1.5Å provide elegant insights into the catalytic mechanism and molecular basis for their three apparently distinct activities. Our data reveal a pre-mRNA 5' end capping quality control mechanism in mammalian cells, indicating DXO as the central player for this mechanism, and demonstrate an unexpected intimate link between proper 5' end capping and subsequent pre-mRNA processing.
PubMed: 23523372
DOI: 10.1016/j.molcel.2013.02.017
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.5 Å)
Structure validation

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