Heat-induced native dimerization prevents amyloid formation by variable domain from immunoglobulin light-chain REI
| Autor: | Mikio Kataoka, Satoru Unzai, Daizo Hamada, Marina Nawata, Shouhei Mine, Yuta Kobayashi, Hironari Kamikubo, Hirotaka Tsutsumi, Tsutomu Nakamura, Koichi Uegaki |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Circular dichroism Amyloid Protein Folding Hot Temperature Stereochemistry Dimer Mutant Immunoglobulin Variable Region Gene Expression Immunoglobulin light chain Crystallography X-Ray Biochemistry Protein Structure Secondary 03 medical and health sciences chemistry.chemical_compound X-Ray Diffraction Scattering Small Angle medicine Native state Escherichia coli Humans Protein Interaction Domains and Motifs Amino Acid Sequence Cloning Molecular Molecular Biology Protein Unfolding Sequence Homology Amino Acid Chemistry Protein Stability Amyloidosis Cell Biology computer.file_format medicine.disease Protein Data Bank Recombinant Proteins Kinetics 030104 developmental biology Monomer Mutation Thermodynamics Immunoglobulin Light Chains Protein Multimerization computer Sequence Alignment |
| Zdroj: | The FEBS journal. 284(18) |
| ISSN: | 1742-4658 |
| Popis: | Amyloid light-chain (AL) amyloidosis is a protein-misfolding disease characterized by accumulation of immunoglobulin light chains (LCs) into amyloid fibrils. Dimerization of a full length or variable domain (VL) of LC serves to stabilize the native state and prevent the formation of amyloid fibrils. We here analyzed the thermodynamic properties of dimerization and unfolding reactions by nonamyloidogenic VL from REI LC or its monomeric Y96K mutant using sedimentation velocity and circular dichroism. The data indicate that the equilibrium shifts to native dimerization for wild-type REI VL by elevating temperature due to the negative enthalpy change for dimer dissociation (−81.2 kJ·mol−1). The Y96K mutation did not affect the stability of the monomeric native state but increased amyloidogenicity. These results suggest that the heat-induced native homodimerization is the major factor preventing amyloid formation by wild-type REI VL. Heat-induced native oligomerization may be an efficient strategy to avoid the formation of misfolded aggregates particularly for thermostable proteins that are used at elevated temperatures under conditions where other proteins tend to misfold. Database Structural data are available in the Protein Data Bank under the accession numbers 5XP1 and 5XQY. |
| Databáze: | OpenAIRE |
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