May 2021: Published in Nuclear Acids Research, Neel Sarovar Bhavesh and collaborators in New Delhi elucidate the molecular basis of the RBMS1-promoter DNA interaction to understand the mechanism for specificity.
Understanding the specificity and affinity of protein-DNA interactions is a long-standing question, involving thermodynamics and kinetics. Evidence, however, remains scarce when answering crucial biological questions.
DNA binding proteins recognize DNA specifically or non-specifically using direct and indirect readout mechanisms like sliding, hopping, and diffusion. However, a common difficulty in explicitly elucidating any particular mechanism of site-specific DNA-protein recognition is the lack of knowledge regarding target sequences and inadequate account of non-specific interactions, in general. In this paper, Aggarwal and Bhavesh have deciphered the structural basis of target search performed by the key regulator of expression of c-myc proto-oncogene, the human RBMS1 protein and have shown the structural reorganization of this multi-domain protein required for recognizing the specific c-myc promoter sequence.
The work provides the first structural and dynamics characterization of human RBMS1 protein that controls the expression of c-myc proto-oncogene inside the human cell by its interaction with 7 base pair consensus sequence within the 21 bp promoter/ autonomous origin of replication region 2 kb upstream of c-myc proto-oncogene.
The results suggest that a synergy between structural re-organization and thermodynamics is necessary for the recognition of target sequences. The study thereby presents another perspective of looking at the DNA-protein interactions.
Aggarwal, P. and Bhavesh, NS. Hingle like domain motion facilitates human RBMS1 protein binding to proto-oncogene c-myc promoter. Nucleic Acids Res (2021). https://doi.org/10.1093/nar/gkab363
neelsb.com/myblog/ Molecular mechanisms of specificity in promoter DNA recognition (English and Hindi)