Molecular Basis of the Mechanisms controlling MASTL.

Molecular Basis of the Mechanisms controlling MASTL. Mol Cell Proteomics. 2019 Dec 18;: Authors: Hermida D, Mortuza GB, Pedersen AK, Pozdnyakova I, Nguyen TTTN, Maroto M, Williamson M, Ebersole T, Cazzamali G, Rand KD, Olsen JV, Malumbres M, Montoya G Abstract The human MASTL (Microtubule-associated serine/threonine kinase-like) gene encodes an essential protein in the cell cycle. MASTL is a key factor preventing early dephosphorylation of M-phase targets of Cdk1/CycB. Little is known about the mechanism of MASTL activation and regulation. MASTL contains a non-conserved insertion of 550 residues within its activation loop, splitting the kinase domain, and making it unique. Here, we show that this non-conserved middle region (NCMR) of the protein is crucial for target specificity and activity. We performed a phosphoproteomic assay with different MASTL constructs identifying key phosphorylation sites for its activation and determining whether they arise from autophosphorylation or exogenous kinases, thus generating an activation model. Hydrogen/deuterium exchange data complements this analysis revealing that the C-lobe in full-length MASTL forms a stable structure, while the N-lobe is dynamic and the NCMR and C-tail contain few localised regions with higher-order structure. Our results indicate that truncated versions of MASTL conserving a cryptic C-Lobe in the NCMR, display catalytic activity and different targets, thus establishing a...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Tags: Mol Cell Proteomics Source Type: research