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Authors
Zhihong Cheng1, Denise Muhlrad2, Meng Kiat Lim1, Roy Parker2, and Haiwei Song1.
1 Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673.
2 Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, University of Arizona, Tucson, AZ 85721, USA.
Abstract
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 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.
Published in The EMBO Journal (2007) 26, 253–264.
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