title: Enhanced conformational flexibility of the histone-like (HU) protein from Mycoplasma gallisepticum.
abstract: The histone-like (HU) protein is one of the major nucleoid-associated proteins involved in DNA supercoiling and compaction into bacterial nucleoid as well as in all DNA-dependent transactions. This small positively charged dimeric protein binds DNA in a non-sequence specific manner promoting DNA super-structures. The majority of HU proteins are highly conserved among bacteria; however, HU protein from Mycoplasma gallisepticum (HUMgal) has multiple amino acid substitutions in the most conserved regions, which are believed to contribute to its specificity to DNA targets unusual for canonical HU proteins. In this work, we studied the structural dynamic properties of the HUMgal dimer by NMR spectroscopy and MD simulations. The obtained all-atom model displays compliance with the NMR data and confirms the heterogeneous backbone flexibility of HUMgal. We found that HUMgal, being folded into a dimeric conformation typical for HU proteins, has a labile α-helical body with protruded β-stranded arms forming DNA-binding domain that are highly flexible in the absence of DNA. The amino acid substitutions in conserved regions of the protein are likely to affect the conformational lability of the HUMgal dimer that can be responsible for complex functional behavior of HUMgal in vivo, e.g. facilitating its spatial adaptation to non-canonical DNA-targets.
authors.affiliation: a National Research Centre 'Kurchatov Institute', Kurchatov Complex of NBICS-Technologies , Akad. Kurchatova sqr., 1, Moscow 123182 , Russian Federation.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Altukhov
authors.affiliation: b Moscow Institute of Physics and Technology , Institutskiy per., 9, Dolgoprudny, Moscow Region 141700 , Russian Federation.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Talyzina
authors.affiliation: a National Research Centre 'Kurchatov Institute', Kurchatov Complex of NBICS-Technologies , Akad. Kurchatova sqr., 1, Moscow 123182 , Russian Federation.
authors.forename: Yulia K
authors.initials: YK
authors.lastname: Agapova
authors.affiliation: a National Research Centre 'Kurchatov Institute', Kurchatov Complex of NBICS-Technologies , Akad. Kurchatova sqr., 1, Moscow 123182 , Russian Federation.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Vlaskina
authors.affiliation: a National Research Centre 'Kurchatov Institute', Kurchatov Complex of NBICS-Technologies , Akad. Kurchatova sqr., 1, Moscow 123182 , Russian Federation.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Korzhenevskiy
authors.affiliation: a National Research Centre 'Kurchatov Institute', Kurchatov Complex of NBICS-Technologies , Akad. Kurchatova sqr., 1, Moscow 123182 , Russian Federation.|c Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry RAS , str. Miklukho-Maklaya 16/10, Moscow 117997 , Russian Federation.
authors.forename: Eduard V
authors.initials: EV
authors.lastname: Bocharov
authors.affiliation: a National Research Centre 'Kurchatov Institute', Kurchatov Complex of NBICS-Technologies , Akad. Kurchatova sqr., 1, Moscow 123182 , Russian Federation.|c Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry RAS , str. Miklukho-Maklaya 16/10, Moscow 117997 , Russian Federation.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Rakitina
authors.affiliation: a National Research Centre 'Kurchatov Institute', Kurchatov Complex of NBICS-Technologies , Akad. Kurchatova sqr., 1, Moscow 123182 , Russian Federation.|d Federal Scientific Research Center 'Crystallography and Photonics' RAS , Leninskii pr., 59, Moscow 119333 , Russian Federation.
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Timofeev
authors.affiliation: a National Research Centre 'Kurchatov Institute', Kurchatov Complex of NBICS-Technologies , Akad. Kurchatova sqr., 1, Moscow 123182 , Russian Federation.|e Bach Institute of Biochemistry , Research Center of Biotechnology of the Russian Academy of Sciences , Leninsky Prospekt. 33, bld. 2, Moscow 119071 , Russian Federation.
authors.forename: Vladimir O
authors.initials: VO
authors.lastname: Popov
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D045686:Mycoplasma gallisepticum / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C040330:histone-like protein HU, bacteria; D004247:DNA
keywords: Mycoplasma gallisepticum; chemical shift assignment; conformation exchange; histone-like protein; protein structure determination