Molecular dynamics simulations to investigate the effects of zinc ions on the structural stability of the c-Cbl RING domain.
In eukaryotic cells, ubiquitylation of proteins plays a critical role in regulating diverse cell processes by the ubiquitin activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin protein ligase (E3). E3 is the key component that confers specificity to ubiquitylation and directs the conjugation of ubiquitin to a specific target protein. RING domains are small structured protein domains that require the coordination of zinc ions for a stable tertiary fold and some of them are involved in the E3 family. In this study, we reported the detailed relationships between the two zinc ions and the structural stability of the c-Cbl RING domain by molecular dynamics simulations. Our results show that these two zinc ions play an important role in maintaining both the secondary and tertiary structural stabilities of the c-Cbl RING domain. Our results also reveal that the secondary structural stability of the c-Cbl RING domain is mainly determined by the hydrogen-bonding networks in or near the two zinc ion binding sites. Our results further demonstrate that zinc ion binding site 2 is more structurally stable than site 1.
Liu
Hsuan-Liang
HL
Department of Chemical Engineering and Biotechnology and Graduate Institute of Biotechnology, National Taipei University of Technology, 1 Section 3 ZhongXiao East Road, Taipei, Taiwan 10608. f10894@ntut.edu.tw
Yang
Ching-Tao
CT
Zhao
Jian-Hua
JH
Huang
Chih-Hung
CH
Lin
Hsin-Yi
HY
Fang
Hsu-Wei
HW
Ho
Yih
Y
Tsai
Wei-Bor
WB
D003198:Computer Simulation; D004795:Enzyme Stability; D007477:Ions; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D050721:Proto-Oncogene Proteins c-cbl / Q000737:chemistry* / Q000648:ultrastructure*; D015032:Zinc / Q000737:chemistry*
D007477:Ions; D050721:Proto-Oncogene Proteins c-cbl; D015032:Zinc