The binding domain structure of retinoblastoma-binding proteins.
The retinoblastoma gene product (Rb), a cellular growth suppressor, complexes with viral and cellular proteins that contain a specific binding domain incorporating three invariant residues: Leu-X-Cys-X-Glu, where X denotes a nonconserved residue. Hydrophobic and electrostatic properties are strongly conserved in this segment even though the nonconserved amino acids vary considerably from one Rb-binding protein to another. In this report, we present a diagnostic computer pattern for a high-affinity Rb-binding domain featuring the three conserved residues as well as the conserved physico-chemical properties. Although the pattern encompasses only 10 residues (with only 4 of these explicitly defined), it exhibits 100% sensitivity and 99.95% specificity in database searches. This implies that a certain pattern of structural and physico-chemical properties encoded by this short sequence is sufficient to govern specific Rb binding. We also present evidence that the secondary structural conformation through this region is important for effective Rb binding.
Department of Medicine, Albany Medical College, New York 12208.
J
J
Figge
K
K
Breese
S
S
Vajda
Q L
QL
Zhu
L
L
Eisele
T T
TT
Andersen
R
R
MacColl
T
T
Friedrich
T F
TF
Smith
D000595:Amino Acid Sequence; D000957:Antigens, Viral, Tumor / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics; D002942:Circular Dichroism; D004268:DNA-Binding Proteins; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D027383:Papillomaviridae / Q000737:chemistry; D010446:Peptide Fragments / Q000138:chemical synthesis; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016160:Retinoblastoma Protein / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013539:Simian virus 40 / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
D000957:Antigens, Viral, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; D016160:Retinoblastoma Protein