title: Isomerization kinetics of AT hook decapeptide solution structures.
abstract: The mammalian high mobility group protein HMGA2 contains three DNA binding motifs associated with many physiological functions including oncogenesis, obesity, stem cell youth, human height, and human intelligence. In the present paper, trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) has been utilized to study the conformational dynamics of the third DNA binding motif using the "AT hook" decapeptide unit (Lys(1)-Arg(2)-Prol(3)-Arg(4)-Gly(5)-Arg(6)-Prol(7)-Arg(8)-Lys(9)-Trp(10), ATHP) as a function of the solvent state. Solvent state distributions were preserved during electrospray ion formation, and multiple IMS bands were identified for the [M + 2H](2+) and for the [M + 3H](3+) charge states. Conformational isomer interconversion rates were measured as a function of the trapping time for the [M + 2H](2+) and [M + 3H](3+) charge states. Candidate structures were proposed for all IMS bands observed. Protonation site, proline residue conformation, and side chain orientations were identified as the main motifs governing the conformational interconversion processes. Conformational dynamics from the solvent state distribution to the gas-phase "de-solvated" state distribution demonstrated that ATHP is "structured", and relative abundances are associated with the relative stability between the proposed conformers. The most stable ATHP [M + 2H](2+) conformation at the "de-solvated" state corresponds to the AT hook motif observed in AT-rich DNA regions.
authors.affiliation: Department of Chemistry and Biochemistry, Florida International University , 11200 SW Eighth Street, AHC4-233, Miami, Florida 33199, United States.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Schenk
authors.forename: Mark E
authors.initials: ME
authors.lastname: Ridgeway
authors.forename: Melvin A
authors.initials: MA
authors.lastname: Park
authors.forename: Fenfei
authors.initials: F
authors.lastname: Leng
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernandez-Lima
mesh_terms: D024761:AT-Hook Motifs; D004247:DNA / Q000737:chemistry; D025743:HMGA2 Protein / Q000737:chemistry*; D006801:Humans; D007536:Isomerism; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D011522:Protons; D012996:Solutions; D021241:Spectrometry, Mass, Electrospray Ionization; D055672:Static Electricity
chemical_list: D025743:HMGA2 Protein; D009842:Oligopeptides; D011522:Protons; D012996:Solutions; D004247:DNA; D011392:Proline