Conformational preferences in the Ser133‐phosphorylated and non‐phosphorylated forms of the kinase inducible transactivation domain of CREB

FEBS Letters

Dyson, H.Jane¹  Pérez-Alvarado, Gabriela C¹  Wright, Peter E¹  Radhakrishnan, Ishwar¹ 

[1] Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA

关键词: Protein phosphorylation;    Conformational change;    Transactivation domain structure;    Nuclear magnetic resonance spectroscopy;    Protein-protein interaction;    Transcription activation;    CREB;    cyclic AMP response element binding protein;    CBP;    CREB binding protein;    KID;    kinase inducible domain;    pKID;    Ser133-phosphorylated KID;    PK-A;    protein kinase-A;    NMR;    nuclear magnetic resonance;    HSQC;    heteronuclear single quantum coherence;    3D;    three-dimensional;    NOESY;    nuclear Overhauser effect spectroscopy;    NOE;    nuclear Overhauser effect;    TOCSY;    total correlation spectroscopy;    CD;    circular dichroism;   

DOI  :  10.1016/S0014-5793(98)00680-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Phosphorylation of Ser¹³³ within the kinase inducible transactivation domain (KID) of the transcription factor CREB potentiates interaction with the KIX domain of coactivator CBP. Heteronuclear NMR spectroscopic analyses reveal that the KID domain is largely unstructured except for residues that comprise the αA helix in the pKID-KIX complex, which populate helical conformations to a significant extent (>50%). The helical content in the αB region is very small in the non-phosphorylated form (∼10%) although a small increase is detected upon Ser¹³³ phosphorylation. The intrinsic bias towards helical conformations probably facilitates folding of the KID domain upon binding to KIX while the principal role of the phosphate group appears to be largely in mediating the intermolecular interactions in the pKID-KIX complex.

【 授权许可】

Unknown