caa a22 4500 477136540 CHVBK 20180405111720.0 cr unu---uuuuu 170330e19970601xx s 000 0 eng 10.1023/A:1018350611521 doi (NATIONALLICENCE)springer-10.1023/A:1018350611521 Hydrogen-deuterium exchange studies of the rat thyroid transcription factor 1 homeodomain [Elektronische Daten] [Gennaro Esposito, Federico Fogolari, Giuseppe Damante, Silvestro Formisano, Gianluca Tell, Antonio Leonardi, Roberto Lauro, Paolo Viglino] The 1H NMR solution structure of the rat thyroidtranscription factor 1 homeodomain (TTF-1 HD) showed that the molecule foldslike classical homeodomains. The C-terminal extension of helix III (fragment51-59) appeared to adopt a helical geometry, albeit not as rigid asthe preceding portion, but the hydrogen-deuterium exchange of backboneamides and the NOE data provided evidence of a discontinuity between the twomoieties of helix III at the highly conserved fragmentAsn51-His52-Arg53.Analysis of quantitative measurements of isotope exchange rates allows oneto recognize the general occurrence, in that region of HD motifs, ofopposite effects to helix III stability. Asparagine, histidine and arginineresidues occur most frequently at the beginning and end of protein helices.In TTF-1 HD a local fluctuation is observed in the fragment 51-53which either kinks or tightens the α-helix. A search through theprotein structure database reveals that the three most common variants of HDfragments 51-53 are often involved in helices and, frequently, inhelix initiation or termination. For homeodomains in general, the nature ofthe fragment 51-53 may be related to the conformational dynamics oftheir DNA-recognition helix (helix III). Besides the specific results onfragment 51-53, the complete isotope exchange analysis of TTF-1 HDdata shows that the partially solvent-exposed recognition helix isstabilized by hydrophobic interactions, like most of the structured regionsof the molecule. Hydrophobic stabilization of the contacting regions meetsthe requirements of a DNA-interaction mechanism which, as shown with otherDNA-protein complexes, should entail negative heat capacity variations dueto changes in solvent exposure of the nonpolar protein surface. Kluwer Academic Publishers, 1997 Thyroid transcription factor 1 homeodomain nationallicence Homeodomain nationallicence DNA-binding proteins nationallicence Protein NMR nationallicence Hydrogen-deuterium exchange nationallicence Secondary structure thermal stability nationallicence Esposito Gennaro Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut Fogolari Federico Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut Damante Giuseppe Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut Formisano Silvestro Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut Tell Gianluca Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut Leonardi Antonio Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut Lauro Roberto Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut Viglino Paolo Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut Journal of Biomolecular NMR Kluwer Academic Publishers 9/4(1997-06-01), 397-407 0925-2738 9:4<397 1997 9 10858 https://doi.org/10.1023/A:1018350611521 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1018350611521 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Esposito Gennaro Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut NATIONALLICENCE 700 1- Fogolari Federico Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut NATIONALLICENCE 700 1- Damante Giuseppe Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut NATIONALLICENCE 700 1- Formisano Silvestro Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut NATIONALLICENCE 700 1- Tell Gianluca Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut NATIONALLICENCE 700 1- Leonardi Antonio Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut NATIONALLICENCE 700 1- Lauro Roberto Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut NATIONALLICENCE 700 1- Viglino Paolo Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Via Gervasutta 48, I-33100, Udine, Italy aut NATIONALLICENCE 773 0- Journal of Biomolecular NMR Kluwer Academic Publishers 9/4(1997-06-01), 397-407 0925-2738 9:4<397 1997 9 10858 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer