2hwx
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| , resolution 1.90Å | |||||||
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| Gene: | EST1A (Homo sapiens) | ||||||
| Related: | 2HWW
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of human SMG6 E1282C PIN domain mutant.
OverviewOverview
SMG6 and SMG5 are essential factors in nonsense-mediated mRNA decay, a conserved pathway that degrades mRNAs with premature translation termination codons. Both SMG5 and SMG6 have been predicted to contain a C-terminal PIN (PilT N-terminus) domain, present in proteins with ribonuclease activity. We have determined the structures of human SMG5 and SMG6 PIN domains. Although they share a similar overall fold related to ribonucleases of the RNase H family, they have local differences at the putative active site. SMG6 has the canonical triad of acidic residues that are crucial in RNase H for nuclease activity, while SMG5 lacks key catalytic residues. The structural differences are reflected at the functional level. Only the PIN domain of SMG6 has degradation activity on single-stranded RNA in vitro. This difference in catalytic activity is conserved in Drosophila, where an SMG6 with an inactive PIN domain inhibits NMD in a dominant-negative manner. Our findings suggest that the NMD machinery has intrinsic nuclease activity that is likely to contribute to the rapid decay of mRNAs that terminate translation prematurely.
About this StructureAbout this Structure
2HWX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex., Glavan F, Behm-Ansmant I, Izaurralde E, Conti E, EMBO J. 2006 Nov 1;25(21):5117-25. Epub 2006 Oct 19. PMID:17053788
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