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Structural and functional insights into the human Upf1 helicase core
Author(s) -
Cheng Zhihong,
Muhlrad Denise,
Lim Meng Kiat,
Parker Roy,
Song Haiwei
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601464
Subject(s) - biology , helicase , computational biology , core (optical fiber) , genetics , microbiology and biotechnology , gene , rna , materials science , composite material
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.