부산대학교 도서관

Human histone deacetylase 6 (HDAC6) is a structurally unique, multidomain protein implicated in a variety of physiological processes including cytoskeletal remodelling and the maintenance of cellular homeostasis. Our current understanding of the HDAC6 structure is limited to isolated domains, and a holistic picture of the full‐length protein structure, including possible domain interactions, is missing. Here, we used an integrative structural biology approach to build a solution model of HDAC6 by combining experimental data from several orthogonal biophysical techniques complemented by molecular modelling. We show that HDAC6 is best described as a mosaic of folded and intrinsically disordered domains that in‐solution adopts an ensemble of conformations without any stable interactions between structured domains. Furthermore, HDAC6 forms dimers/higher oligomers in a concentration‐dependent manner, and its oligomerization is mediated via the positively charged N‐terminal microtubule‐binding domain. Our findings provide the first insights into the structure of full‐length human HDAC6 and can be used as a basis for further research into structure function and physiological studies of this unique deacetylase. [ABSTRACT FROM AUTHOR]