pISSN 2288-6982
eISSN 2288-7105




BioDesign 2021; 9(2): 25-31

Published online June 30, 2021

© Korean Society for Structural Biology

Comparative analysis of CSL-binding motifs of SMRT and KyoT2 corepressors

Gwang Sik Kim and Young Chul Lee*

School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Republic of Korea

Correspondence to: *

Received: February 7, 2021; Revised: March 25, 2021; Accepted: March 25, 2021


Notch signaling plays a fundamental role in the regulation of diverse biological processes. In the absence of Notch signaling, DNA-bound CSL [CBF1/Su(H)/Lag-1] factor represses gene expression via the direct recruitment of corepressor proteins, including silencing mediator of retinoid and thyroid receptor (SMRT) and KyoT2. Structural studies have unveiled the molecular basis of these interactions in which corepressors bind to CSL using a conserved ΦWΦP motif (Φ: any hydrophobic residues). Here, we comparatively analyzed the CSL-binding motifs of SMRT (1830EHAPIWRP1837) and KyoT2 (186VKAPVWWP193) using swap mutants. Various in vivo and in vitro binding assays confirmed that V186 and W192 residues of KyoT2 are major determinants for high affinity binding to CSL. We designed a peptide with the chimeric sequence (VHAPIWWP) of CSL-binding motifs of SMRT and KyoT2. Intriguingly, this peptide acts as an in vivo competitor of endogenous corepressor proteins and an artificial activator for the transcriptional activity of NICD.

Graphical Abstract