2mh3
NMR structure of the basic helix-loop-helix region of the transcriptional repressor HES-1
Structural highlights
FunctionHES1_HUMAN Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity (By similarity). May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage.[1] Publication Abstract from PubMedHES-1, one of the main downstream effectors in Notch signaling, is a transcriptional repressor of the basic helix-loop-helix (bHLH) family. Using NMR methods, we have determined the structure and dynamics of a recombinant protein, H1H, which includes an N-terminal segment, b1, containing functionally important phosphorylation sites, the basic region b2, required for binding to DNA, and the helix-loop-helix domain (HLH). We show that a proline residue in the sequence divides the protein in two parts, a flexible and disordered N-terminal region including b1 and a structured, mainly helical region comprising b2 and the HLH domain. Binding of H1H to a dsDNA oligonucleotide was monitored through the chemical shift perturbation of backbone amide resonances, and showed that the interaction surface involves not only the b2 segment, but also several residues in the b1 and HLH regions. (c) Proteins 2014;. (c) 2014 Wiley Periodicals, Inc. The basic-helix-loop-helix region of the transcriptional repressor HES-1 is preorganized to bind DNA.,Popovic M, Wienk H, Coglievina M, Boelens R, Pongor S, Pintar A Proteins. 2014 Jan 8. doi: 10.1002/prot.24507. PMID:24403087[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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