Open interface and large quaternary structure movements in 3D domain swapped proteins: Insights from molecular dynamics simulations of the C-terminal swapped dimer of ribonuclease
Open interface and large quaternary structure movements in 3D domain swapped proteins: Insights from molecular dynamics simulations of the C-terminal swapped dimer of ribonuclease(759 views) Merlino A, Ceruso MA, Vitagliano L, Mazzarella L
Keywords: Dimer, Monomer, Pancreatic Ribonuclease, Protein Subunit, Multiprotein Complex, Alpha Helix, Amino Terminal Sequence, Article, Beta Sheet, Calculation, Carboxy Terminal Sequence, Enzyme Activity, Enzyme Stability, Enzyme Structure, Molecular Dynamics, Molecular Interaction, Molecular Recognition, Motion, Nonhuman, Protein Aggregation, Protein Assembly, Protein Domain, Protein Folding, Protein Protein Interaction, Protein Quaternary Structure, Simulation, Structure Analysis, X Ray Crystallography, Binding Site, Chemical Model, Chemical Structure, Chemistry, Computer Simulation, Dimerization, Protein Binding, Protein Conformation, Ultrastructure, Bovinae, Protein Structure,
Affiliations: *** IBB - CNR ***
Centro Interdipartimentale Ricerca e Management, Complesso Ristrutturato S. Andrea Delle Dame, 80138, Naples, Italy
Dipartimento di Chimica, Università degli Studi di Napoli Federico II, 80125 Naples, Italy
Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY, United States
Istituto di Biostrutture e Bioimmagini, CNR, 80134 Naples, Italy
References: Not available.
Open interface and large quaternary structure movements in 3D domain swapped proteins: Insights from molecular dynamics simulations of the C-terminal swapped dimer of ribonuclease
Bovine pancreatic ribonuclease ( RNase A) forms two three-dimensional (3D) domain swapped dimers. Crystallographic investigations have revealed that these dimers display completely different quaternary structures: one dimer (N-dimer), which presents the swapping of the N-terminal helix, is characterized by a compact structure, whereas the other (C-dimer), which is stabilized by the exchange of the C- terminal end, shows a rather loose assembly of the two subunits. The dynamic properties of monomeric RNase A and of the N-dimer have been extensively characterized. Here, we report a molecular dynamics investigation carried out on the C- dimer. This computational experiment indicates that the quaternary structure of the C- dimer undergoes large. uctuations. These motions do not perturb the proper folding of the two subunits, which retain the dynamic properties of RNase A and the N-dimer. Indeed, the individual subunits of the C- dimer display the breathing motion of the beta-sheet structure, which is important for the enzymatic activity of pancreatic- like ribonucleases. In contrast to what has been observed for the N-dimer, the breathing motion of the two subunits of the C- dimer is not coupled. This finding suggests that the intersubunit communications in a 3D domain swapped dimer strongly rely on the extent of the interchain interface. Furthermore, the observation that the C- dimer is endowed with a high intrinsic flexibility holds interesting implications for the specific properties of 3D domain swapped dimers. Indeed, a survey of the quaternary structures of the other 3D domain swapped dimers shows that large variations are often observed when the structural determinations are conducted in different experimental conditions. The 3D domain swapping phenomenon coupled with the high flexibility of the quaternary structure may be relevant for protein-protein recognition, and in particular for the pathological aggregations.
Open interface and large quaternary structure movements in 3D domain swapped proteins: Insights from molecular dynamics simulations of the C-terminal swapped dimer of ribonuclease
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Open interface and large quaternary structure movements in 3D domain swapped proteins: Insights from molecular dynamics simulations of the C-terminal swapped dimer of ribonuclease