The effect of D380Y pathogenic mutation in human Yin Yang 1 on the protein’s structure and function

Małgorzata Figiel; Julia Łakomska; Marta Dziedzicka-Wasylewska; Andrzej Górecki

doi:10.18388/abp.2020_2911

Małgorzata Figiel Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland https://orcid.org/0000-0001-9390-7418
Julia Łakomska Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland
Marta Dziedzicka-Wasylewska Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland
Andrzej Górecki Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland https://orcid.org/0000-0002-4159-447X

DOI: https://doi.org/10.18388/abp.2020_2911

Abstract

Yin Yang 1 is a human transcription factor that controls a number of genes and takes part in the regulation of cell cycle, proliferation, differentiation, and neuronal development. Yin Yang 1 is composed of an N-terminal intrinsically disordered fragment and a C-terminal domain responsible for binding to DNA, composed of four zinc fingers. Recently, various alterations in the Yin Yang 1’s DNA binding domain were linked with an unexplained intellectual disability named Gabriele-de Vries syndrome. In this paper, a repetitively occurring substitution of aspartate-380 for tyrosine was analyzed to assess its impact on Yin Yang 1’s structure and DNA binding. The substitution was found to affect Yin Yang 1’s secondary and tertiary structure to a limited extent and to impair the specificity of its interaction with DNA.