The native metastability and misfolding of serine protease inhibitors.
The native metastability of serine protease inhibitors (serpins) is believed to facilitate the conformational change required for biological function. However, energetically unfavorable structural features that contribute to metastability of the native serpin conformation, such as buried polar groups, cavities, and over-packing of side-chains, also appear to hinder proper folding. Hence, folding of serpin polypeptides appears prone to error; in particular, the folding polypeptides are readily diverted toward a non-productive folding pathway culminating in a more stable but inactive conformation. In a survey of deficient serpin mutants, various folding defects, such as retarded protein folding, destabilized native conformation, and spontaneous conversion into more stable, inactive conformations such as the latent form and loop-sheet polymers, have been discovered.
Cho
Ye-Lim
YL
Department of Molecular Biology and Applied Chemistry, Research Center for Conformational Degenerative Diseases, Sejong University, 98 Gunja-dong, Kwangjin-gu, Seoul 143-747, Korea.
Chae
Young Kee
YK
Jung
Chan-Hun
CH
Kim
Min-Jung
MJ
Na
Yu-Ran
YR
Kim
Yang-Hee
YH
Kang
Shin-Jung
SJ
Im
Hana
H
D000682:Amyloid / Q000096:biosynthesis; D007700:Kinetics; D009154:Mutation; D011108:Polymers / Q000737:chemistry; D017510:Protein Folding; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000502:physiology*; D015843:Serpins / Q000737:chemistry* / Q000502:physiology*; D013329:Structure-Activity Relationship
D000682:Amyloid; D011108:Polymers; D015842:Serine Proteinase Inhibitors; D015843:Serpins