Impact factor: 1.427, Impact factor a 5 anni: 3.227
Url: Non disponibile.
Parole chiave: Domain Swapping
, Loop Regions
, Molecular Dynamics
, Protein Aggregation
, Protein Engineering
, Protein Stabilization
, X-Ray Crystallography
*** IBB - CNR *** CNR Istituto di Biostrutture e Bioimmagini, Via Mezzocannone 16, I-80134 Napoli, Italy. Electronic address: email@example.com. Dipartimento di Scienze Chimiche, Universita degli Studi di Napoli "Federico II", Via Cintia, I-80126 Napoli, Italy.
Structural roles of loop regions are frequently overlooked in proteins. Nevertheless, they may be key players in the definition of protein topology and in the self-assembly processes occurring through domain swapping. We here investigate the effects on structure and stability of replacing the loop connecting the last two beta-strands of RNase A with the corresponding region of the more thermostable Onconase. The crystal structure of this chimeric variant (RNaseA-ONC) shows that its terminal loop size better adheres to the topological rules for the design of stabilized proteins, proposed by Baker and coworkers . Indeed, RNaseA-ONC displays a thermal stability close to that of RNase A, despite the lack of Pro at position 114, which, due to its propensity to favor a cis peptide bond, has been identified as an important stabilizing factor of the native protein. Accordingly, RNaseA-ONC is significantly more stable than RNase A variants lacking Pro114; RNaseA-ONC also displays a higher propensity to form oligomers in native conditions when compared to either RNase A or Onconase. This finding demonstrates that modifications of terminal loops should to be carefully controlled in terms of size and sequence to avoid unwanted and/or potentially harmful aggregation processes.<br>
27 Records (27 escludendo Abstract e Conferenze). Impact factor totale: 84.294 (84.294 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 80.036 (80.036 escludendo Abstract e Conferenze).