A single amino acid exchange transfers VP16-induced positive control from the Oct-1 to the Oct-2 homeo domain

Lai, J. S., Cleary, M. A., Herr, W. (November 1992) A single amino acid exchange transfers VP16-induced positive control from the Oct-1 to the Oct-2 homeo domain. Genes Dev, 6 (11). pp. 2058-65. ISSN 0890-9369 (Print)0890-9369 (Linking)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/1358756
DOI: 10.1101/gad.6.11.2058


The selective association of the herpesvirus trans-activator VP16 with the human Oct-1 homeo domain is a model for differential positive transcriptional control by homeo domains. VP16 discriminates between the closely related homeo domains of Oct-1 and Oct-2 by distinguishing among their seven amino-acid differences; these differences lie on the surface that is thought to be accessible when the homeo domain is bound to DNA. Only two of these seven differences are recognized by VP16, one in each of the first two alpha-helices of the tri-alpha-helical homeo domain. The major determinant for selective association with VP16 in vitro and VP16-induced positive control in vivo is a single glutamic acid residue at position 22 in the first alpha-helix of the Oct-1 homeo domain, but the acidic properties of this residue are not critical for association with VP16 in vitro or in vivo, because it can be replaced by glutamine with little or no deleterious effect. Mere replacement of the single corresponding alanine residue in the Oct-2 homeo domain with the key glutamic acid residue is sufficient to confer on the Oct-2 homeo domain the ability to associate with VP16 in vitro and respond to VP16-induced positive control in vivo. Thus, the specificity of homeo domain positive control can be conferred by a single amino acid difference.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Base Sequence DNA-Binding Proteins/*metabolism *Genes, Homeobox Herpes Simplex Virus Protein Vmw65/genetics/*metabolism Host Cell Factor C1 Humans Models, Molecular Molecular Sequence Data Octamer Transcription Factor-1 Octamer Transcription Factor-2 Oligonucleotide Probes Protein Structure, Secondary Simplexvirus/genetics/metabolism Structure-Activity Relationship Trans-Activators/*metabolism Transcription Factors/*metabolism Transcription, Genetic
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
organism description > virus > herpes simplex virus
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > homeodomain protein
CSHL Authors:
Communities: CSHL labs > Herr lab
Depositing User: Matt Covey
Date: November 1992
Date Deposited: 01 Oct 2015 16:45
Last Modified: 03 Nov 2017 20:47
Related URLs:
URI: https://repository.cshl.edu/id/eprint/31796

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