?B-Crystallin is a member of the small Heat Shock Protein (HSP) family. ?B-Crystallin simpler multimeric form is an homodimer, while more complex structures can be hollow globes composed from up to 40 monomers (the greatest homooligomer validated atomic model obtained is a 24-mer, Fig. 1a). This HSP is modulated by a trade-off between its different multimeric conformations: in particular, the active units are small complexes, like the hexamers (Fig. 1b), which are torus-like structures composed by 3 dimers connected via an interdimeric interface, while larger conformations are almost inactive. The multimerization of ?B-Crystallin, and thus its function, is controlled by the phosphorylation of two serine residues, Ser45 and Ser59 (Fig. 1c). They localize near the interdimeric interface, which supports the idea that phosphorylations influence the aggregation of dimers in higher structures. With the aim of studying the ?B-Crystallin multimerization, in this work we evaluate the phosphorylation effect on protein structures by molecular dynamics (MD). In particular, our purpose was to link different phosphorylation patterns to the diverse behaviours of the ?B-Crystallin in the 24meric state, using data collected from MD simulations of different multimeric structures. A previous analysis based on dimers II and hexamers MD simulations, identified 5 phosphorilation clusters (Fig2.): the first include phosphorylation patterns comparable to dimers with all P-ser, while the fifth includes pattern comparable to the non-P dimers. Dimers and hexamers structures were undergone to 30 ns of MD simulation at 300 K with Gromacs 4.5, employing the amber99sbP force field, which includes an energy model for phosphoserines. Moreover, three MD simulations of 100ns were obtained for the 24-mer: the first one without phosphorilation and the other two with a combination of promising phosphorylation patterns identified in the analysis of the phosphorylated dimer II.

Effect of serine phosphorylation on aB-Crystallin interface multimeric form

Federica CHIAPPORI;Luciano MILANESI;Ivan MERELLI
2016

Abstract

?B-Crystallin is a member of the small Heat Shock Protein (HSP) family. ?B-Crystallin simpler multimeric form is an homodimer, while more complex structures can be hollow globes composed from up to 40 monomers (the greatest homooligomer validated atomic model obtained is a 24-mer, Fig. 1a). This HSP is modulated by a trade-off between its different multimeric conformations: in particular, the active units are small complexes, like the hexamers (Fig. 1b), which are torus-like structures composed by 3 dimers connected via an interdimeric interface, while larger conformations are almost inactive. The multimerization of ?B-Crystallin, and thus its function, is controlled by the phosphorylation of two serine residues, Ser45 and Ser59 (Fig. 1c). They localize near the interdimeric interface, which supports the idea that phosphorylations influence the aggregation of dimers in higher structures. With the aim of studying the ?B-Crystallin multimerization, in this work we evaluate the phosphorylation effect on protein structures by molecular dynamics (MD). In particular, our purpose was to link different phosphorylation patterns to the diverse behaviours of the ?B-Crystallin in the 24meric state, using data collected from MD simulations of different multimeric structures. A previous analysis based on dimers II and hexamers MD simulations, identified 5 phosphorilation clusters (Fig2.): the first include phosphorylation patterns comparable to dimers with all P-ser, while the fifth includes pattern comparable to the non-P dimers. Dimers and hexamers structures were undergone to 30 ns of MD simulation at 300 K with Gromacs 4.5, employing the amber99sbP force field, which includes an energy model for phosphoserines. Moreover, three MD simulations of 100ns were obtained for the 24-mer: the first one without phosphorilation and the other two with a combination of promising phosphorylation patterns identified in the analysis of the phosphorylated dimer II.
2016
Istituto di Tecnologie Biomediche - ITB
?B-Crystallin
HSP
post-translational modifications
molecular dynamics
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/383332
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