Structural and functional insights into the human Upf1 helicase core

被引:127
作者
Cheng, Zhihong
Muhlrad, Denise
Lim, Meng Kiat
Parker, Roy [1 ]
Song, Haiwei
机构
[1] Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA
[2] Univ Arizona, Howard Hughes Med Inst, Tucson, AZ 85721 USA
[3] Inst Mol & Cell Biol, Lab Macromol Struct, Singapore, Singapore
关键词
mRNA decay; nonsense-mediated mRNA decay; RNA helicase; Upf1; X-ray crystallography;
D O I
10.1038/sj.emboj.7601464
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:253 / 264
页数:12
相关论文
共 40 条
  • [1] A faux 3′-UTR promotes aberrant termination and triggers nonsense-mediated mRNA decay
    Amrani, N
    Ganesan, R
    Kervestin, S
    Mangus, DA
    Ghosh, S
    Jacobson, A
    [J]. NATURE, 2004, 432 (7013) : 112 - 118
  • [2] Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein
    Applequist, SE
    Selg, M
    Raman, C
    Jack, HM
    [J]. NUCLEIC ACIDS RESEARCH, 1997, 25 (04) : 814 - 821
  • [3] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY
    BAILEY, S
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 : 760 - 763
  • [4] Nonsense-mediated mRNA decay: terminating erroneous gene expression
    Baker, KE
    Parker, R
    [J]. CURRENT OPINION IN CELL BIOLOGY, 2004, 16 (03) : 293 - 299
  • [5] Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay
    Bhattacharya, A
    Czaplinski, K
    Trifillis, P
    He, F
    Jacobson, A
    Peltz, SW
    [J]. RNA, 2000, 6 (09) : 1226 - 1235
  • [6] The mRNA surveillance protein hSMG-1 functions in genotoxic stress response pathways in mammalian cells
    Brumbaugh, KM
    Otterness, DM
    Geisen, C
    Oliveira, V
    Brognard, J
    Li, XJ
    Lejeune, F
    Tibbetts, RS
    Maquat, LE
    Abraham, RT
    [J]. MOLECULAR CELL, 2004, 14 (05) : 585 - 598
  • [7] Crystallography & NMR system:: A new software suite for macromolecular structure determination
    Brunger, AT
    Adams, PD
    Clore, GM
    DeLano, WL
    Gros, P
    Grosse-Kunstleve, RW
    Jiang, JS
    Kuszewski, J
    Nilges, M
    Pannu, NS
    Read, RJ
    Rice, LM
    Simonson, T
    Warren, GL
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 : 905 - 921
  • [8] Helicase structure and mechanism
    Caruthers, JM
    McKay, DB
    [J]. CURRENT OPINION IN STRUCTURAL BIOLOGY, 2002, 12 (01) : 123 - 133
  • [9] Nonsense-mediated mRNA decay: molecular insights and mechanistic variations across species
    Conti, E
    Izaurralde, E
    [J]. CURRENT OPINION IN CELL BIOLOGY, 2005, 17 (03) : 316 - 325
  • [10] IDENTIFICATION AND CHARACTERIZATION OF GENES THAT ARE REQUIRED FOR THE ACCELERATED DEGRADATION OF MESSENGER-RNAS CONTAINING A PREMATURE TRANSLATIONAL TERMINATION CODON
    CUI, Y
    HAGAN, KW
    ZHANG, SA
    PELTZ, SW
    [J]. GENES & DEVELOPMENT, 1995, 9 (04) : 423 - 436