2HWW

Structure of PIN domain of human SMG6

Summary for 2HWW

• Entry DOI: 10.2210/pdb2hww/pdb
• Descriptor: Telomerase-binding protein EST1A (2 entities in total)
• Functional Keywords: degradation, decay, nmd, est1a, p bodies, rna binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus, nucleolus: Q86US8
• Total number of polymer chains: 3
• Total formula weight: 61778.10

Authors

Glavan, F.,Behm-Ansmant, I.,Izaurralde, E.,Conti, E. (deposition date: 2006-08-02, release date: 2006-11-14, Last modification date: 2023-08-30)

Primary citation

Glavan, F.,Behm-Ansmant, I.,Izaurralde, E.,Conti, E.
Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex.
Embo J., 25:5117-5125, 2006

PubMed Abstract: 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.

PubMed: 17053788
DOI: 10.1038/sj.emboj.7601377

Experimental method

X-RAY DIFFRACTION (1.8 Å)