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| Subject Categories: Structural Biology |
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| The EMBO Journal
(2007) 26, 253–264, doi:10.1038/sj.emboj.7601464 Published online 7 December 2006 |
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| Structural and functional insights into the human Upf1 helicase core |
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| Zhihong Cheng1, Denise Muhlrad2, Meng Kiat Lim1, Roy Parker2 and Haiwei Song1 |
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1 Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, Singapore, Singapore 2 Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, University of Arizona, Tucson, AZ, USA To whom correspondence should be addressed Roy Parker, Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, University of Arizona, Tucson, AZ 85721, USA. Tel.: +1 520 621 4504; Fax: +1 520 621 4524; E-mail: rrparker@email.arizona.edu Haiwei Song, Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore. Tel.: +65 6586 9700; Fax: +65 6779 1117; E-mail: haiwei@imcb.a-star.edu.sg Received 23 May 2006; Accepted 6 November 2006; Published online 7 December 2006. |
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| Abstract |
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| 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. |
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| Keywords: mRNA decay, nonsense-mediated mRNA decay, RNA helicase, Upf1, X-ray crystallography |
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