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| - | [[Image:2h6w.gif|left|200px]]<br /> | + | #REDIRECT [[3gws]] This PDB entry is obsolete and replaced by 3gws |
| - | <applet load="2h6w" size="450" color="white" frame="true" align="right" spinBox="true"
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| - | caption="2h6w, resolution 2.30Å" />
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| - | '''Thyroid hormone receptor bound to T3'''<br />
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| - | ==Overview==
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| - | The thyroid hormone receptor (TR) D-domain links the ligand-binding domain, (LBD, EF-domain) to the DNA-binding domain (DBD, C-domain), but its, structure, and even its existence as a functional unit, are controversial., The D domain is poorly conserved throughout the nuclear receptor family, and was originally proposed to comprise an unfolded hinge that facilitates, rotation between the LBD and the DBD. Previous TR LBD structures, however, have indicated that the true unstructured region is three to six amino, acid residues long and that the D-domain N terminus folds into a short, amphipathic alpha-helix (H0) contiguous with the DBD and that the C, terminus of the D-domain comprises H1 and H2 of the LBD. Here, we solve, structures of TR-LBDs in different crystal forms and show that the N, terminus of the TRalpha D-domain can adopt two structures; it can either, fold into an amphipathic helix that resembles TRbeta H0 or form an, unstructured loop. H0 formation requires contacts with the AF-2, coactivator-binding groove of the neighboring TR LBD, which binds H0, sequences that resemble coactivator LXXLL motifs. Structural analysis of a, liganded TR LBD with small angle X-ray scattering (SAXS) suggests that, AF-2/H0 interactions mediate dimerization of this protein in solution. We, propose that the TR D-domain has the potential to form functionally, important extensions of the DBD and LBD or unfold to permit TRs to adapt, to different DNA response elements. We also show that mutations of the D, domain LXXLL-like motif indeed selectively inhibit TR interactions with an, inverted palindromic response element (F2) in vitro and TR activity at, this response element in cell-based transfection experiments.
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| - | ==Disease==
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| - | Known diseases associated with this structure: Thyroid hormone resistance OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190160 190160]], Thyroid hormone resistance, autosomal recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190160 190160]]
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| - | ==About this Structure==
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| - | 2H6W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with T3 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2H6W OCA].
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| - | ==Reference==
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| - | Structural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor function., Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Neto M, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov I, J Mol Biol. 2006 Jul 14;360(3):586-98. Epub 2006 May 19. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16781732 16781732]
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| - | [[Category: Homo sapiens]]
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| - | [[Category: Single protein]]
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| - | [[Category: Ambrosio, A.L.B.]]
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| - | [[Category: Aparicio, R.]]
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| - | [[Category: Baxter, J.D.]]
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| - | [[Category: Bleicher, L.]]
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| - | [[Category: Craievich, A.F.]]
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| - | [[Category: Dias, S.M.G.]]
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| - | [[Category: Figueira, A.C.M.]]
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| - | [[Category: Fischer, H.]]
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| - | [[Category: Garrat, R.C.]]
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| - | [[Category: Nascimento, A.S.]]
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| - | [[Category: Neto, M.O.]]
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| - | [[Category: Nunes, F.M.]]
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| - | [[Category: Polikarpov, I.]]
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| - | [[Category: Santos, M.A.M.]]
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| - | [[Category: Togashi, H.F.M]]
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| - | [[Category: Webb, P.]]
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| - | [[Category: T3]]
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| - | [[Category: nuclear receptor]]
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| - | [[Category: t3]]
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| - | [[Category: thyroid]]
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| - | [[Category: tr]]
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| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:27:53 2007''
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