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Characterization of the binding interactions of AT hook motif variants
Author(s) -
Dobbins Kaitlyn R.,
Buchmueller Karen L.
Publication year - 2018
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.2018.32.1_supplement.652.8
Subject(s) - amino acid , dna , biology , computational biology , peptide sequence , gene , consensus sequence , binding site , dna binding site , minor groove , dna binding protein , transcription factor , sequence motif , genetics , microbiology and biotechnology , promoter , gene expression
High Mobility Group A (HMGA) proteins are a family of architectural transcription factors that control expression of many genes and their overexpression has been linked to metastasis in numerous cancers. HMGA binds to the minor groove of AT‐rich DNA through three positively‐charged AT hook motifs, each containing the invariant sequence Arg‐Gly‐Arg‐Pro. We endeavor to investigate the effects of changing the amino acids flanking this invariant sequence. Peptides were designed to have varying flanking sequences based on amino acid occurrences in human AT hook proteins. Variations in binding affinities and structural characteristics of these sequences were elucidated using fluorimetry, circular dichroism, and filter binding. Analysis of these variations reveals which amino acids and which amino acid positions in the sequence may be critical to the binding interactions between the AT hook and DNA. These conclusions will inform the development of HMGA‐targeting therapeutics. Support or Funding Information Arnold and Mabel Beckman Foundation This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .