Thermodynamic origins of protein folding, allostery, and capsid formation in the human hepatitis B virus core protein.

ABSTRACT: HBc, the capsid-forming "core protein" of human hepatitis B virus (HBV), is a multidomain, α-helical homodimer that aggressively forms human HBV capsids. Structural plasticity has been proposed to be important to the myriad functions HBc mediates during viral replication. Here, we report detailed thermodynamic analyses of the folding of the dimeric HBc protomer under conditions that prevented capsid formation. Central to our success was the use of ion mobility spectrometry-mass spectrometry and microscale thermophoresis, which allowed folding mechanisms to be characterized using just micrograms of protein. HBc folds in a three-state transition with a stable, dimeric, α-helical intermediate. Extensive protein engineering showed thermodynamic linkage between different structural domains. Unu

SUBMITTER: Alexander CG 

PROVIDER: S-EPMC3725087 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature