Structural mass spectrometry decodes domain interaction and dynamics of the full-length Human Histone Deacetylase 2.

Human Histone Deacetylase 2 (HDAC2) belongs to a conserved enzyme superfamily that regulates deacetylation inside cells. HDAC2 is a drug target as it is known to be upregulated in cancers and neurodegenerative disorders. It consists of globular deacetylase and C-terminus intrinsically-disordered domains [1-3].

Modeling Protein Complexes Using Restraints from Crosslinking Mass Spectrometry.

Modeling macromolecular assemblies with restraints from crosslinking mass spectrometry (XL-MS) tends to focus solely on distance violation. Recently, we identified three different modeling features inherent in crosslink data: (1) expected distance between crosslinked residues; (2) violation of the crosslinker's maximum bound; and (3) solvent accessibility of crosslinked residues. Here, we implement these features in a scoring function.

Jwalk and MNXL web server: model validation using restraints from crosslinking mass spectrometry.

Motivation: Crosslinking Mass Spectrometry generates restraints that can be used to model proteins and protein complexes. Previously, we have developed two methods, to help users achieve better modelling performance from their crosslinking restraints: Jwalk, to estimate solvent accessible distances between crosslinked residues and MNXL, to assess the quality of the models based on these distances.

Results: Here, we present the Jwalk and MNXL webservers, which streamline the process of validating monomeric protein models using restraints from crosslinks.