Structural and functional insights into the human Upf1 helicase core.
Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance pathway that recognizes and degrades aberrant mRNAs containing premature stop codons. A critical protein in NMD is Upf1p, which belongs to the helicase super family 1 (SF1), and is thought to utilize the energy of ATP hydrolysis to promote transitions in the structure of RNA or RNA-protein complexes. The crystal structure of the catalytic core of human Upf1p determined in three states (phosphate-, AMPPNP- and ADP-bound forms) reveals an overall structure containing two RecA-like domains with two additional domains protruding from the N-terminal RecA-like domain. Structural comparison combined with mutational analysis identifies a likely single-stranded RNA (ssRNA)-binding channel, and a cycle of conformational change coupled to ATP binding and hydrolysis. These conformational changes alter the likely ssRNA-binding channel in a manner that can explain how ATP binding destabilizes ssRNA binding to Upf1p.
Cheng
Zhihong
Z
Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, Singapore, Singapore.
Muhlrad
Denise
D
Lim
Meng Kiat
MK
Parker
Roy
R
Song
Haiwei
H
D000244:Adenosine Diphosphate / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry*; D000495:Allosteric Site; D001665:Binding Sites; D003062:Codon; D018360:Crystallography, X-Ray; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D008968:Molecular Conformation; D009711:Nucleotides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D020365:RNA Helicases; D015534:Trans-Activators / Q000737:chemistry* / Q000502:physiology*
D003062:Codon; D009711:Nucleotides; D015534:Trans-Activators; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D020365:RNA Helicases; C101828:UPF1 protein, human