The solution structure of the human retinoic acid receptor-beta DNA-binding domain.
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.
Department of Chemistry, University of Utrecht, The Netherlands.
R M
RM
Knegtel
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M
Katahira
J G
JG
Schilthuis
A M
AM
Bonvin
R
R
Boelens
D
D
Eib
P T
PT
van der Saag
R
R
Kaptein
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003850:Deoxyribonuclease I; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015183:Restriction Mapping; D014212:Tretinoin / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D014212:Tretinoin; D004247:DNA; D003850:Deoxyribonuclease I