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EMBO J. 2007 Jan 10;26(1):253-64. Epub 2006 Dec 7.

Structural and functional insights into the human Upf1 helicase core.

Author information

1
Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, Singapore, Singapore.

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 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.

PMID:
17159905
PMCID:
PMC1782376
DOI:
10.1038/sj.emboj.7601464
[Indexed for MEDLINE]
Free PMC Article

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