ISSN:
1573-5001
Schlagwort(e):
Thyroid transcription factor 1 homeodomain
;
Homeodomain
;
DNA-binding proteins
;
Protein NMR;
;
Hydrogen–deuterium exchange
;
Secondary structure thermal stability
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Biologie
,
Chemie und Pharmazie
Notizen:
Abstract 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.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1023/A:1018350611521
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