The solution structure of the human retinoic acid receptor-beta DNA-binding domain

J Biomol NMR. 1993 Jan;3(1):1-17. doi: 10.1007/BF00242472.

Abstract

The three-dimensional structure of the DNA-binding domain of the human retinoic acid receptor-beta (hRAR-beta) has been determined by nuclear magnetic resonance spectroscopy in conjunction with distance geometry, restrained molecular dynamics and iterative relaxation matrix calculations. A total of 1244 distance restraints were obtained from NOE intensities, of which 448 were intra-residue and 796 inter-residue restraints. In addition 23 chi and 30 phi dihedral angle restraints were obtained from J-coupling data. The two 'zinc-finger' regions of the 80-amino acid residue protein are followed by two alpha-helices that cross each other perpendicularly. There is a short stretch of b-sheet near the N-terminus. The alpha-helical core of the protein is well determined with a backbone root-mean-square deviation (r.m.s.d.) with respect to the average of 0.18 A and 0.37 A when the side chains of residues 31, 32, 36, 61, 62, 65 and 69 are included. The r.m.s.d. for the backbone of residues 5-80 is 0.76 A. For the first finger (residues 8-28), the r.m.s.d. of the backbone is 0.79 A. For the second finger (residues 44-62) the r.m.s.d. is 0.64 A. The overall structure is similar to that of the corresponding domain of the glucocorticoid receptor, although the C-terminal part of the protein is different. The second alpha-helix is two residues shorter and is followed by a well-defined region of extended backbone structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cloning, Molecular
  • DNA / chemistry
  • DNA / metabolism*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Deoxyribonuclease I
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary*
  • Receptors, Retinoic Acid
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Restriction Mapping
  • Tretinoin / metabolism
  • Zinc Fingers / genetics

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Receptors, Retinoic Acid
  • Recombinant Proteins
  • Tretinoin
  • DNA
  • Deoxyribonuclease I