X-ray crystal structure of an IκBβ•NF-κB p65 homodimer complex

被引:101
作者
Malek, S
Huang, DB
Huxford, T
Ghosh, S
Ghosh, G
机构
[1] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
[2] Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06520 USA
[3] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA
关键词
D O I
10.1074/jbc.M301022200
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
We report the crystal structure of a murine IkappaBbeta.NF-kappaB p65 homodimer complex. Crystallographic models were determined for two triclinic crystalline systems and refined against data at 2.5 and 2.1 Angstrom. The overall complex structure is similar to that of the IkappaBalpha.NF-kappaB p50/p65 heterodimer complex. One NF-kappaB p65 subunit nuclear localization signal clearly contacts IkappaBbeta, whereas a homologous segment from the second subunit of the homodimer is mostly solvent-exposed. The unique 47-amino acid insertion between ankyrin repeats three and four of IkappaBbeta is mostly disordered in the structure. Primary sequence analysis and differences in the mode of binding at the IkappaBbeta sixth ankyrin repeat and NF-kappaB p65 homodimer suggest a model for nuclear IkappaBbeta.NF-kappaB.DNA ternary complex formation. These unique structural features of IkappaBbeta may contribute to its ability to mediate persistent NF-kappaB activation.
引用
收藏
页码:23094 / 23100
页数:7
相关论文
共 55 条
  • [41] NICHOLLS A, 1993, BIOPHYS J, V64, pA166
  • [42] Processing of X-ray diffraction data collected in oscillation mode
    Otwinowski, Z
    Minor, W
    [J]. MACROMOLECULAR CRYSTALLOGRAPHY, PT A, 1997, 276 : 307 - 326
  • [43] Regulation of I kappa B beta in WEHI 231 mature B cells
    Phillips, RJ
    Ghosh, S
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (08) : 4390 - 4396
  • [44] Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a
    Russo, AA
    Tong, L
    Lee, JO
    Jeffrey, PD
    Pavletich, NP
    [J]. NATURE, 1998, 395 (6699) : 237 - 243
  • [45] The ankyrin repeat: a diversity of interactions on a common structural framework
    Sedgwick, SG
    Smerdon, SJ
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1999, 24 (08) : 311 - 316
  • [46] NF-KAPPA-B CONTROLS EXPRESSION OF INHIBITOR I-KAPPA-B-ALPHA - EVIDENCE FOR AN INDUCIBLE AUTOREGULATORY PATHWAY
    SUN, SC
    GANCHI, PA
    BALLARD, DW
    GREENE, WC
    [J]. SCIENCE, 1993, 259 (5103) : 1912 - 1915
  • [47] Suyang H, 1996, MOL CELL BIOL, V16, P5444
  • [48] Cytoplasmic sequestration of Rel proteins by IκBα requires CRM1-dependent nuclear export
    Tam, WF
    Lee, LH
    Davis, L
    Sen, R
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (06) : 2269 - 2284
  • [49] IκB family members function by different mechanisms
    Tam, WF
    Sen, RJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (11) : 7701 - 7704
  • [50] CLUSTAL-W - IMPROVING THE SENSITIVITY OF PROGRESSIVE MULTIPLE SEQUENCE ALIGNMENT THROUGH SEQUENCE WEIGHTING, POSITION-SPECIFIC GAP PENALTIES AND WEIGHT MATRIX CHOICE
    THOMPSON, JD
    HIGGINS, DG
    GIBSON, TJ
    [J]. NUCLEIC ACIDS RESEARCH, 1994, 22 (22) : 4673 - 4680