Document Detail


Structural and functional analysis of the NF-kappa B p65 C terminus. An acidic and modular transactivation domain with the potential to adopt an alpha-helical conformation.
MedLine Citation:
PMID:  7929265     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The p65 subunit of the NF-kappa B transcription factor contains in its C-terminal 120 amino acids at least two transcription activation domains. One domain (TA1) is contained within only the 30 C-terminal amino acids. Structural studies employing CD and NMR spectroscopy revealed that the TA1 domain is unstructured. NMR analysis of a protein corresponding to the C-terminal 123 amino acids also showed a random coil conformation. However, a portion of TA1 was found to adopt an alpha-helical conformation in the presence of hydrophobic solvents. Transcriptional analysis of point mutants revealed the functional importance of two evolutionary conserved sequence repeats, which are located in the conditionally alpha-helical region of TA1. These repeats acted synergistically in transcription activation. The inhibitory effect of some mutants indicated secondary structure constraints on TA1 in intact cells. Inverting the sequence of two acidic activation domains significantly reduced their transactivating potential, suggesting that amino acid composition is not solely essential for activity; a defined primary structure is necessary as well. Acidic sequence motifs related in primary structure and squelching activity to those of TA1 are present in the activation domains of VP16, c-Rel, and several other transcription factors. We propose a model suggesting that primarily unstructured acidic activation domains can adopt a secondary structure upon contacting their target molecules by an "induced fit" mechanism.
Authors:
M L Schmitz; M A dos Santos Silva; H Altmann; M Czisch; T A Holak; P A Baeuerle
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  269     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1994 Oct 
Date Detail:
Created Date:  1994-11-17     Completed Date:  1994-11-17     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  25613-20     Citation Subset:  IM    
Affiliation:
Institute for Biochemistry, Albert Ludwigs University, Freiburg, Federal Republic of Germany.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Cells, Cultured
DNA Mutational Analysis
Fungal Proteins / metabolism
Humans
Models, Molecular
Molecular Sequence Data
NF-kappa B / genetics,  metabolism*
Protein Structure, Secondary*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-rel
Recombinant Proteins / metabolism
Repetitive Sequences, Nucleic Acid / genetics
Sequence Homology, Amino Acid
Spectrophotometry, Ultraviolet
Structure-Activity Relationship
Trans-Activators / metabolism
Transcription Factor RelA
Transcriptional Activation*
Chemical
Reg. No./Substance:
0/Fungal Proteins; 0/Gal-VP16; 0/NF-kappa B; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-rel; 0/Recombinant Proteins; 0/Trans-Activators; 0/Transcription Factor RelA

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