Molecular basis for dimer formation of TRbeta variant D355R.

Article Details


Jouravel N, Sablin E, Togashi M, Baxter JD, Webb P, Fletterick RJ

Molecular basis for dimer formation of TRbeta variant D355R.

Proteins. 2009 Apr;75(1):111-7. doi: 10.1002/prot.22225.

PubMed ID
18798561 [ View in PubMed

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 A resolution with R(free)/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 A(2) characteristic for a strong complex assembly that is additionally strengthened by buffer solutes.

DrugBank Data that Cites this Article

NameUniProt ID
Thyroid hormone receptor betaP10828Details