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THE FOLDING AND BINDING PATHWAY OF THE TRANSCRIPTION FACTOR CREB TO CBP
Author(s) -
Turjanski Adrian Gustavo,
Best Robert,
Hummer Gerhard,
Gutkind J Silvio
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a270-a
Subject(s) - creb , transcription factor , microbiology and biotechnology , activator (genetics) , general transcription factor , transcription (linguistics) , biology , binding site , creb1 , computational biology , chemistry , promoter , genetics , gene expression , gene , linguistics , philosophy
A central tenet of genomics is that sequence determines structure, and structure determines function. Even though this is true for most proteins, in the last years an increasing number of proteins have been found that are natively unfolded. For many of these proteins, this intrinsic disorder appears to be required for their function. Many transcription factors have been experimentally observed to be unstructured in solution. Transcription factors are central components of intracellular regulatory networks that control the expression of genes involved in a variety of biological processes, ranging from cell proliferation and differentiation to migration, and their aberrant activity can result in tumorigenesis. The cAMP‐response element binding protein (CREB) is one of the best characterized transcription factors in terms of structure and function. The phosphorylation of CREB promotes recruitment of the transcriptional co‐activator CBP (CREB Binding Protein). CREB binds to CBP by undergoing a transition from unstructured to structure that has been an archetype for the study of concomitant folding and binding. Here, we have studied the folding and binding mechanism of CREB to KIX by simulation of a topology‐based model. Our results give a complete picture of the folding and binding process and allow the reinterpretation of previous experimental results.