Abstract
The linker histone is a component of the nucleosome, which is the repeating unit of chromatin. It has pronounced heterogeneity in higher eukaryotes. It has a tripartite structure consisting of a well-structured globular domain flanked by intrinsically unstructured C- and N-terminal domains (C- and NTD, respectively). The linker histone is a multifunctional protein and this property is thought to be attributed to the intrinsically unstructured domains of which the NTD is the least studied. The NTD is also thought to play a major role in the characteristic binding affinity of the H1 variants. Structural studies on NTDs of two murine H1 variants suggest inducible secondary structures that may be linked to DNA binding. The structural elements were induced by TFE in vitro. Whilst these studies gave valuable insight into the structure of the NTD, the number of H1 variants included in these studies was not representative of H1 heterogeneity. The current study investigated structure forming propensities of NTDs of nine human H1 variants in an effort to establish distinguishing structural elements between the H1 variants. Bioinformatics tools were used to predict secondary structure propensity of the NTDs from which four were selected for further structural characterisation. TFE and NaClO4 were used as secondary structure stabilizers to characterise the inducible structural elements of the NTDs. This was done by CD and FTIR spectroscopy...
M.Sc. (Biochemistry)