Structure of the carboxy-terminal region of thyroid hormone nuclear receptors and its possible role in hormone-dependent intermolecular interactions

Biochemistry
M K BhatS Cheng

Abstract

The thyroid hormone nuclear receptors (TRs) are ligand-dependent transcription factors. To understand the molecular basis of ligand-dependent transactivation, we studied the structure of their carboxy-terminal activation domain. We analyzed the structures of the peptides derived from the C-terminal sequences of human TR subtypes beta 1 (h-TR beta 1) and alpha 1 (h-TR alpha 1) and a human TR mutant, PV, by circular dichroism (CD). Mutant PV has a C-terminal frameshift mutation and does not bind to the thyroid hormone, 3,3',5-triiodo-L-thyronine (T3). Analyses of the secondary structures of the peptides by CD indicate that five amino acids, EVFED, are part of an amphipathic alpha-helix which is required to maintain the structural integrity of the hormone binding domain. A monoclonal antibody, C4 (mAb C4), which recognizes both h-TR beta 1 and h-TR alpha 1 was developed. Using a series of truncated mutants and synthetic peptides, we mapped the epitope of mAb C4 to the conserved C-terminal amino acids, EVFED. Analysis of the binding data indicates that binding of T3 to either h-TR beta 1 or h-TR alpha 1 was competitively inhibited by mAb C4. Deletion of C-terminal amino acids including EVFED led to a total loss of T3 binding activi...Continue Reading

References

May 25, 1992·Proceedings of the National Academy of Sciences of the United States of America·L Zhong, W C Johnson
Jun 1, 1991·The Journal of Clinical Investigation·V K ChatterjeeJ L Jameson
Dec 18, 1986·Nature·C WeinbergerR M Evans
Dec 18, 1986·Nature·S Green, P Chambon
Sep 9, 1986·Biochemistry·K PrasadM S Lewis
Feb 2, 1971·Biochemistry·J E Brown, W A Klee
Jan 6, 1981·Biochemistry·S W Provencher, J Glöckner
Aug 31, 1993·Biochemical and Biophysical Research Communications·M K BhatS Y Cheng
Apr 1, 1995·Journal of Biomedical Science·S.-y. Cheng Sy

❮ Previous
Next ❯

Citations

Feb 1, 1996·Nature Structural Biology·J M WurtzH Gronemeyer
Jan 16, 2007·Molecular and Cellular Biology·Hao YingSheue-Yann Cheng
Oct 14, 2006·The Journal of Clinical Investigation·Hao YingSheue-Yann Cheng
Mar 11, 2011·Journal of Molecular Endocrinology·Xu-Guang ZhuSheue-Yann Cheng
Jan 19, 2010·Journal of Molecular Endocrinology·Alok MishraSheue-Yann Cheng
Jul 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·A DaceS Cheng
Nov 9, 2000·Proceedings of the National Academy of Sciences of the United States of America·M KaneshigeS Cheng
Nov 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Osamu ArakiSheue-Yann Cheng
Jun 6, 2002·The Journal of Biological Chemistry·Huei-Min LinSheue-Yann Cheng
Jan 1, 1996·Nature Structural Biology·J M WurtzH Gronemeyer
Feb 14, 1997·The Journal of Biological Chemistry·Y T TingS y Cheng
Nov 20, 1997·The Journal of Biological Chemistry·M K BhatS Cheng
Jun 1, 1997·Thyroid : Official Journal of the American Thyroid Association·Y T Ting, S Y Cheng
Dec 4, 2020·Thyroid : Official Journal of the American Thyroid Association·Sunmi ParkSheue-Yann Cheng

❮ Previous
Next ❯