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Updated: Jul 14, 2025
Characterization of Multi-subunit Protein Complexes of Human MxA Using Non-denaturing Polyacrylamide Gel-electrophoresis
Published on: October 28, 2016
M Protein from Dengue virus oligomerizes to pentameric channel protein: in silico analysis study
Ayesha Zeba1, Kanagaraj Sekar2, Anjali Ganjiwale1
1Department of Life Sciences, Bangalore University, Bangalore, Karnataka 560056, India.
Abstract:
The Dengue virus M protein is a 75 amino acid polypeptide with two helical transmembranes (TM). The TM domain oligomerizes to form an ion channel, facilitating viral release from the host cells. The M protein has a critical role in the virus entry and life cycle, making it a potent drug target. The oligomerization of the monomeric protein was studied using ab initio modeling and molecular dynamics (MD) simulation in an implicit membrane environment. The representative structures obtained showed pentamer as the most stable oligomeric state, resembling an ion channel. Glutamic acid, threonine, serine, tryptophan, alanine, isoleucine form the pore-lining residues of the pentameric channel, conferring an overall negative charge to the channel with approximate length of 51.9 Å. Residue interaction analysis (RIN) for M protein shows that Ala94, Leu95, Ser112, Glu124, and Phe155 are the central hub residues representing the physicochemical interactions between domains. The virtual screening with 165 different ion channel inhibitors from the ion channel library shows monovalent ion channel blockers, namely lumacaftor, glipizide, gliquidone, glisoxepide, and azelnidipine to be the inhibitors with high docking scores. Understanding the three-dimensional structure of M protein will help design therapeutics and vaccines for Dengue infection.
Insights
The Dengue virus M protein forms a pentameric ion channel crucial for viral release. This structure reveals potential drug targets for developing new Dengue virus therapeutics.
Area of Science:
- Structural Biology
- Virology
- Computational Biology
Background:
- The Dengue virus M protein is a key component in the viral life cycle.
- Its transmembrane domain oligomerizes to form an ion channel essential for viral release.
- The M protein's role makes it a significant target for antiviral drug development.
Purpose of the Study:
- To investigate the oligomerization of the Dengue virus M protein.
- To elucidate the structural characteristics of the M protein ion channel.
- To identify potential inhibitors of the M protein ion channel.
Main Methods:
- Ab initio modeling and molecular dynamics (MD) simulations were employed.
- Simulations were conducted in an implicit membrane environment.
- Virtual screening of ion channel inhibitors was performed against the M protein model.
Main Results:
- The M protein was found to form a stable pentameric ion channel.
- Pore-lining residues confer a net negative charge; the channel is approximately 51.9 Å long.
- Residue interaction analysis identified key hub residues (Ala94, Leu95, Ser112, Glu124, Phe155).
- Monovalent ion channel blockers like lumacaftor and glipizide showed high docking scores.
Conclusions:
- The pentameric M protein structure resembles an ion channel, critical for Dengue virus function.
- Understanding the M protein's three-dimensional structure aids in designing targeted therapeutics and vaccines.
- Specific ion channel blockers demonstrate potential for inhibiting Dengue virus propagation.
