Recognition of the helix-loop-helix domain of the Id proteins by an artificial luminescent metal complex receptor.
Synthetic agents specifically interacting with a protein interface are important not only for the better understanding of protein dimer or complex formation but also for medical applications. Here we describe the recognition of the helix-loop-helix (HLH) dimerization domain of the Id proteins by an artificial luminescent receptor containing two binding sites for a Lewis acid and a Lewis base, respectively. The Id proteins are inhibitors of bHLH transcription factors and play key roles during development of cancer. We show that a receptor/Id-HLH-domain complex was formed cooperatively (K(0.5) approximately 2 microM under physiological conditions) and with moderate specificity, as compared to the related MyoD and Max HLH domains. Accordingly, a preferred receptor binding motif, CYSR(K), was identified within the Id HLH domains. These results are promising and may be exploited to design highly selective synthetic receptors for the Id HLH domain.
Kiewitz
Sebastian D
SD
Fakultät für Chemie und Pharmazie, Universität Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany.
Kruppa
Michael
M
Riechers
Alexander
A
König
Burkhard
B
Cabrele
Chiara
C
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D005453:Fluorescence; D018257:Helix-Loop-Helix Motifs; D051796:Inhibitor of Differentiation Proteins / Q000737:chemistry* / Q000378:metabolism*; D049449:Luminescence; D008670:Metals / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017186:Titrimetry
D051796:Inhibitor of Differentiation Proteins; D008670:Metals; D010455:Peptides