Premium
Elucidation of the ribonuclease a aggregation process mediated by 3D domain swapping: A computational approach reveals possible new multimeric structures
Author(s) -
Cozza Giorgio,
Moro Stefano,
Gotte Giovanni
Publication year - 2008
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20833
Subject(s) - trimer , chemistry , conformational isomerism , rnase p , rnase h , protein subunit , supramolecular chemistry , crystallography , ribonuclease , bovine pancreatic ribonuclease , domain (mathematical analysis) , stereochemistry , molecule , rna , dimer , biochemistry , crystal structure , mathematical analysis , mathematics , organic chemistry , gene
By lyophilization from 40% acetic acid solutions, bovine pancreatic ribonuclease A forms several three‐dimensional (3D) domain‐swapped oligomers: dimers, trimers, tetramers, pentamers, hexamers, and traces of high‐order oligomers, purifiable by cation‐exchange chromatography. Each oligomeric species consists of at least two conformers displaying different basicity density, and/or exposure of positive charges. The structures of the two dimers and one trimer have been solved. Plausible models have been proposed for a second RNase A trimer and four tetramers, but not all the models are certainly assignable to the tetramers purified. Further studies have also been made on the pentameric and hexameric species, again without reaching structurally clear‐cut results. This work is focused on the detailed modeling of the tetrameric RNase A species, using four different approaches to possibly clarify unknown structural aspects. The results obtained do not confirm the validity of one tetrameric model previously proposed, but allow the proposal of a novel tetrameric structure displaying new interfaces that are absent in the other known conformers. New details concerning other tetrameric structures are also described. RNase A multimers larger than tetramers, i.e., pentamers, hexamers, octamers, nonamers, up to dodecamers, are also modeled, with the proposal of novel domain‐swapped structures, and the confirmation of what had previously been inferred. Finally, the propensity of RNase A to possibly form high‐order supramolecular multimers is analyzed starting from the large number of domain‐swapped RNase A conformers modeled. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 26–39, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com