Molecular basis for dimer formation of TRβ variant D355R

Natalia Jouravel, Elena Sablin, Marie Togashi, John D. Baxter, Paul Webb, Robert J. Fletterick

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Protein quality and stability are critical during protein purification for X-ray crystallography. A target protein that is easy to manipulate and crystallize becomes a valuable product useful for high-throughput crystallography for drug design and discovery. In this work, a single surface mutation, D355R, was shown to be crucial for converting the modestly stable monomeric ligand binding domain of the human thyroid hormone receptor (TR LBD) into a stable dimer. The structure of D335R TR LBD mutant was solved using X-ray crystallography and refined to 2.2 Å resolution with Rfree/R values of 24.5/21.7. The crystal asymmetric unit reveals the TR dimer with two molecules of the hormone-bound LBD related by twofold symmetry. The ionic interface between the two LBDs comprises residues within loop H10-H11 and loop H6-H7 as well as the C-terminal halves of helices 8 of both protomers. Direct intermolecular contacts formed between the introduced residue Arg 355 of one TR molecule and Glu 324 of the second molecule become a part of the extended dimerization interface of 1330 Å2 characteristic for a strong complex assembly that is additionally strengthened by buffer solutes.

Original languageEnglish (US)
Pages (from-to)111-117
Number of pages7
JournalProteins: Structure, Function and Bioinformatics
Issue number1
StatePublished - Apr 2009


  • Crystal structure
  • Homo-dimer
  • Ligand binding domain
  • Protein purification
  • Thyroid hormone receptor

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Molecular Biology


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