N-helix and Cysteines Inter-regulate Human Mitochondrial VDAC-2 Function and Biochemistry
| Autor: | Svetlana Rajkumar Maurya, Radhakrishnan Mahalakshmi |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Gene isoform
N-terminal domain Voltage-dependent anion channel Gating Biochemistry Protein Structure Secondary Mitochondrial Proteins Structure-Activity Relationship thermodynamics protein folding Humans membrane protein Cysteine Molecular Biology Ion channel voltage-dependent anion channel (VDAC) biology Voltage-Dependent Anion Channel 2 Chemistry Transporter Cell Biology Membrane protein Protein Structure and Folding gating ion channel biology.protein Protein folding Ion Channel Gating Function (biology) |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m115.693978 |
| Popis: | Human voltage-dependent anion channel-2 (hVDAC-2) functions primarily as the crucial anti-apoptotic protein in the outer mitochondrial membrane, and additionally as a gated bidirectional metabolite transporter. The N-terminal helix (NTH), involved in voltage sensing, bears an additional 11-residue extension (NTE) only in hVDAC-2. In this study, we assign a unique role for the NTE as influencing the chaperone-independent refolding kinetics and overall thermodynamic stability of hVDAC-2. Our electrophysiology data shows that the N-helix is crucial for channel activity, whereas NTE sensitizes this isoform to voltage gating. Additionally, hVDAC-2 possesses the highest cysteine content, possibly for regulating reactive oxygen species content. We identify interdependent contributions of the N-helix and cysteines to channel function, and the measured stability in micellar environments with differing physicochemical properties. The evolutionary demand for the NTE in the presence of cysteines clearly emerges from our biochemical and functional studies, providing insight into factors that functionally demarcate hVDAC-2 from the other VDACs. |
| Databáze: | OpenAIRE |
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