Back to Search
Start Over
The effects of R683S (G) genetic mutations on the JAK2 activity, structure and stability.
- Source :
-
International journal of biological macromolecules [Int J Biol Macromol] 2013 Sep; Vol. 60, pp. 186-95. Date of Electronic Publication: 2013 Jun 05. - Publication Year :
- 2013
-
Abstract
- Janus kinase 2 (JAK2) is an important mediator of cytokine receptor signaling and plays key roles in the hematopoietic and immune response. The acquired JAK2 R683S (G) mutations are presumed to be a biomarker for B-cell acute lymphoblastic leukemia (B-ALL). However, how these mutations leading to the B-ALL is still unclear. The crystal structure of JAK2 JH2 domain suggests that the residue R683 locating in the linker between the N and C lobes of JH2 domain is important for keeping the compact structure, activity and structural stability of this domain. Mutations R683S, R683G and R683E significantly increase JAK2 activity and decrease its structural stability. While the R683K and R683H mutations almost have no effects on the JAK2 activity and structural stability. Furthermore, the spectroscopic experiments imply that mutations R683S, R683G and R683E impair the structure of JAK2 JH2 domain, and lead JAK2 to partially unfolded state. It may be this partially unfolded state that caused JAK2 R683S (G) constitutive activation. This study provides clues in understanding the mechanism of JAK2 R683S (G) mutations caused B-ALL.<br /> (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Subjects :
- Amino Acid Substitution
Enzyme Activation
Enzyme Stability
Humans
Janus Kinase 2 chemistry
Kinesis
Models, Molecular
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism
Protein Conformation
Protein Folding
Structure-Activity Relationship
Thermodynamics
Janus Kinase 2 genetics
Janus Kinase 2 metabolism
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 60
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 23748007
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2013.05.029