Microscale thermophoresis analysis of the molecular interaction between small nuclear ribonucleoprotein polypeptide G and the RING finger domain of RBBP6 towards anti-cancer drug discovery

Lloyd Mabonga; Priscilla Masamba; Albertus Kotze Basson; Abidemi Paul Kappo

Microscale thermophoresis analysis of the molecular interaction between small nuclear ribonucleoprotein polypeptide G and the RING finger domain of RBBP6 towards anti-cancer drug discovery

Am J Transl Res. 2021 Nov 15;13(11):12775-12785. eCollection 2021.

Authors

Lloyd Mabonga¹, Priscilla Masamba², Albertus Kotze Basson¹, Abidemi Paul Kappo²

Affiliations

¹ Department of Biochemistry and Microbiology, University of Zululand KwaDlangezwa 3886, South Africa.
² Molecular Biophysics and Structural Biology (MBSB) Group, Department of Biochemistry, Faculty of Science, University of Johannesburg, Kingsway Campus Auckland Park 2006, South Africa.

PMID: 34956492
PMCID: PMC8661184

Abstract

Regulatory core-splicing proteins are now becoming highly promising therapeutic targets for the development of anti-cancer drugs. SNRPG and RBBP6 are two good examples of regulatory core-splicing proteins involved in tumorigenesis and tumor development whose multi-functional role is primarily mediated by protein-protein interactions. Over the years, skepticism abutting from the two onco-proteins has been mounting. Suggestive evidence using yeast 2-hybrid technique observed possible involvement between SNRPG and the RING finger domain of RBBP6. However, the putative interaction remains elusive and yet to be characterized. In this study, we developed the first MST-based assay to confirm the interaction between SNRPG and the RING finger domain of RBBP6. The results demonstrated a strong binding affinity between SNRPG and the RING finger domain of RBBP6 with a K_D in the low nanomolar concentration range of 3.1596 nM. The results are congruent with previous findings suggesting possible involvement between the two proteins in cancer-cell networks, thereby providing a new mechanistic insight into the interaction between SNRPG and the RING finger domain of RBBP6. The interaction is therapeutically relevant and represents a great milestone in the anti-cancer drug discovery space. Identification of small molecule inhibitors to modulate the binding affinity between the two proteins would therefore be a major breakthrough in the development of new PPI-focused anti-cancer drugs.

Keywords: Anti-cancer drug discovery; RBBP6; RING finger; SNPRG; cancer; microscale thermophoresis.