{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Garabedian A"],"funding":["National institute of Allergy and Infectious Diseases","NIAID NIH HHS","National Institutes of General Medicine","NIGMS NIH HHS","National Science Foundation"],"pagination":["2431-2439"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8934665"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["50(5)"],"pubmed_abstract":["The mammalian high mobility group protein AT-hook 2 (HMGA2) houses three motifs that preferentially bind short stretches of AT-rich DNA regions. These DNA binding motifs, known as 'AT-hooks', are traditionally characterized as being unstructured. Upon binding to AT-rich DNA, they form ordered assemblies. It is this disordered-to-ordered transition that has implicated HMGA2 as a protein actively involved in many biological processes, with abnormal HMGA expression linked to a variety of health problems including diabetes, obesity, and oncogenesis. In the current work, the solution binding dynamics of the three 'AT-hook' peptides (ATHPs) with AT-rich DNA hairpin substrates were studied using DNA UV melting studies, fluorescence spectroscopy, native ion mobility spectrometry-mass spectrometry (IMS-MS), solution isothermal titration calorimetry (ITC) and molecular modeling. Results showed that the ATHPs bind to the DNA to form a single, 1:1 and 2:1, 'key-locked' conformational ensemble. The molecular models showed that 1:1 and 2:1 complex formation is driven by the capacity of the ATHPs to bind to the minor and major grooves of the AT-rich DNA oligomers. Complementary solution ITC results confirmed that the 2:1 stoichiometry of ATHP: DNA is originated under native conditions in solution."],"journal":["Nucleic acids research"],"pubmed_title":["AT-hook peptides bind the major and minor groove of AT-rich DNA duplexes."],"pmcid":["PMC8934665"],"funding_grant_id":["R21 AI125973","1R21AI125973","R01 GM134247","R01GM134247","CHE-1654274"],"pubmed_authors":["Jeanne Dit Fouque K","Fernandez-Lima F","Chapagain PP","Leng F","Garabedian A"],"additional_accession":[]},"is_claimable":false,"name":"AT-hook peptides bind the major and minor groove of AT-rich DNA duplexes.","description":"The mammalian high mobility group protein AT-hook 2 (HMGA2) houses three motifs that preferentially bind short stretches of AT-rich DNA regions. These DNA binding motifs, known as 'AT-hooks', are traditionally characterized as being unstructured. Upon binding to AT-rich DNA, they form ordered assemblies. It is this disordered-to-ordered transition that has implicated HMGA2 as a protein actively involved in many biological processes, with abnormal HMGA expression linked to a variety of health problems including diabetes, obesity, and oncogenesis. In the current work, the solution binding dynamics of the three 'AT-hook' peptides (ATHPs) with AT-rich DNA hairpin substrates were studied using DNA UV melting studies, fluorescence spectroscopy, native ion mobility spectrometry-mass spectrometry (IMS-MS), solution isothermal titration calorimetry (ITC) and molecular modeling. Results showed that the ATHPs bind to the DNA to form a single, 1:1 and 2:1, 'key-locked' conformational ensemble. The molecular models showed that 1:1 and 2:1 complex formation is driven by the capacity of the ATHPs to bind to the minor and major grooves of the AT-rich DNA oligomers. Complementary solution ITC results confirmed that the 2:1 stoichiometry of ATHP: DNA is originated under native conditions in solution.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-04-08T18:05:44.317Z","creation":"2025-04-05T22:18:56.664Z"},"accession":"S-EPMC8934665","cross_references":{"pubmed":["35212375"],"doi":["10.1093/nar/gkac115"]}}