Abstract
Human cyclin A 2 participates in cell cycle regulation, DNA replication, and transcription. Its overexpression has been implicated in the development and progression of a variety of human cancers. However, cyclin A 2 or its truncated form is very unstable in the absence of binding partner, which makes it difficult to get a deep insight of structural basis of the interactions. Therefore, biophysical studies of the full-length human cyclin A 2 would provide important information regarding protein stability and folding/unfolding process. To the best of our knowledge, these have not been reported. In this report, we found that cyclin A 2 stability depended on pH, salt concentration, and denaturant concentration, and low concentration denaturant increased cyclin A 2 stability studied by UV melting, fluorescence spectroscopy, limited proteolysis, and circular dichroism. The therrmal unfolding/folding process could be described by Lumry-Eyring model: N <--> I --> D, followed by decreasing alpha-helix content and forming intermolecular antiparallel pleated beta-sheet structures in the aggregate. Our results are of importance for studying the interactions between cyclin A 2 and therapeutic agents, such as small molecules or peptides, because cyclin A 2 is very unstable in the absence of its biological associated kinases.
Published Version
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