Interaction of monomeric Ebola VP40 protein with a plasma membrane: a coarse-grained molecular dynamics (CGMD) simulation study

Ebola virus is a lipid-enveloped filamentous virus that affects human and non-human primates and consists of several types of protein: nucleoprotein, VP30, VP35, L protein, VP40, VP24, and transmembrane glycoprotein. Among the Ebola virus proteins, its matrix protein VP40 is abundantly expressed dur...

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Main Authors:	Mohamad Yusoff, Mohamad Ariff, Abdul Hamid, Azzmer Azzar, Muhamad Bunnori, Noraslinda, Abd Halim, Khairul Bariyyah
Format:	Article
Language:	English English English
Published:	Elsevier 2018
Subjects:	Q Science (General)
Online Access:	http://irep.iium.edu.my/63665/ http://irep.iium.edu.my/63665/ http://irep.iium.edu.my/63665/ http://irep.iium.edu.my/63665/7/63665%20Interaction%20of%20monomeric%20Ebola%20VP40%20protein%20SCOPUS.pdf http://irep.iium.edu.my/63665/13/63665_Interaction%20of%20monomeric%20Ebola%20VP40%20protein.pdf http://irep.iium.edu.my/63665/19/63665_Interaction%20of%20monomeric%20Ebola%20VP40%20protein%20with%20a%20plasma.pdf

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spelling	iium-636652019-01-03T02:39:58Z http://irep.iium.edu.my/63665/ Interaction of monomeric Ebola VP40 protein with a plasma membrane: a coarse-grained molecular dynamics (CGMD) simulation study Mohamad Yusoff, Mohamad Ariff Abdul Hamid, Azzmer Azzar Muhamad Bunnori, Noraslinda Abd Halim, Khairul Bariyyah Q Science (General) Ebola virus is a lipid-enveloped filamentous virus that affects human and non-human primates and consists of several types of protein: nucleoprotein, VP30, VP35, L protein, VP40, VP24, and transmembrane glycoprotein. Among the Ebola virus proteins, its matrix protein VP40 is abundantly expressed during infection and plays a number of critical roles in oligomerization, budding and egress from the host cell. VP40 exists predominantly as a monomer at the inner leaflet of the plasma membrane, and has been suggested to interact with negatively charged lipids such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylserine (PS) via its cationic patch. The hydrophobic loop at the C-terminal domain has also been shown to be important in the interaction between the VP40 and the membrane. However, details of the molecular mechanisms underpinning their interactions are not fully understood. This study aimed at investigating the effects of mutation in the cationic patch and hydrophobic loop on the interaction between the VP40 monomer and the plasma membrane using coarse-grained molecular dynamics simulation (CGMD). Our simulations revealed that the interaction between VP40 and the plasma membrane is mediated by the cationic patch residues. This led to the clustering of PIP2 around the protein in the inner leaflet as a result of interactions between some cationic residues including R52, K127, K221, K224, K225, K256, K270, K274, K275 and K279 and PIP2 lipids via electrostatic interactions. Mutation of the cationic patch or hydrophobic loop amino acids caused the protein to bind at the inner leaflet of the plasma membrane in a different orientation, where no significant clustering of PIP2 was observed around the mutated protein. This study provides basic understanding of the interaction of the VP40 monomer and its mutants with the plasma membrane. Elsevier 2018-06 Article PeerReviewed application/pdf en http://irep.iium.edu.my/63665/7/63665%20Interaction%20of%20monomeric%20Ebola%20VP40%20protein%20SCOPUS.pdf application/pdf en http://irep.iium.edu.my/63665/13/63665_Interaction%20of%20monomeric%20Ebola%20VP40%20protein.pdf application/pdf en http://irep.iium.edu.my/63665/19/63665_Interaction%20of%20monomeric%20Ebola%20VP40%20protein%20with%20a%20plasma.pdf Mohamad Yusoff, Mohamad Ariff and Abdul Hamid, Azzmer Azzar and Muhamad Bunnori, Noraslinda and Abd Halim, Khairul Bariyyah (2018) Interaction of monomeric Ebola VP40 protein with a plasma membrane: a coarse-grained molecular dynamics (CGMD) simulation study. Journal of Molecular Graphics and Modeling, 82. pp. 137-144. ISSN 1093-3263 https://www.sciencedirect.com/science/article/pii/S1093326317309427 10.1016/j.jmgm.2018.04.010
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English English
topic	Q Science (General)
spellingShingle	Q Science (General) Mohamad Yusoff, Mohamad Ariff Abdul Hamid, Azzmer Azzar Muhamad Bunnori, Noraslinda Abd Halim, Khairul Bariyyah Interaction of monomeric Ebola VP40 protein with a plasma membrane: a coarse-grained molecular dynamics (CGMD) simulation study
description	Ebola virus is a lipid-enveloped filamentous virus that affects human and non-human primates and consists of several types of protein: nucleoprotein, VP30, VP35, L protein, VP40, VP24, and transmembrane glycoprotein. Among the Ebola virus proteins, its matrix protein VP40 is abundantly expressed during infection and plays a number of critical roles in oligomerization, budding and egress from the host cell. VP40 exists predominantly as a monomer at the inner leaflet of the plasma membrane, and has been suggested to interact with negatively charged lipids such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylserine (PS) via its cationic patch. The hydrophobic loop at the C-terminal domain has also been shown to be important in the interaction between the VP40 and the membrane. However, details of the molecular mechanisms underpinning their interactions are not fully understood. This study aimed at investigating the effects of mutation in the cationic patch and hydrophobic loop on the interaction between the VP40 monomer and the plasma membrane using coarse-grained molecular dynamics simulation (CGMD). Our simulations revealed that the interaction between VP40 and the plasma membrane is mediated by the cationic patch residues. This led to the clustering of PIP2 around the protein in the inner leaflet as a result of interactions between some cationic residues including R52, K127, K221, K224, K225, K256, K270, K274, K275 and K279 and PIP2 lipids via electrostatic interactions. Mutation of the cationic patch or hydrophobic loop amino acids caused the protein to bind at the inner leaflet of the plasma membrane in a different orientation, where no significant clustering of PIP2 was observed around the mutated protein. This study provides basic understanding of the interaction of the VP40 monomer and its mutants with the plasma membrane.
format	Article
author	Mohamad Yusoff, Mohamad Ariff Abdul Hamid, Azzmer Azzar Muhamad Bunnori, Noraslinda Abd Halim, Khairul Bariyyah
author_facet	Mohamad Yusoff, Mohamad Ariff Abdul Hamid, Azzmer Azzar Muhamad Bunnori, Noraslinda Abd Halim, Khairul Bariyyah
author_sort	Mohamad Yusoff, Mohamad Ariff
title	Interaction of monomeric Ebola VP40 protein with a plasma membrane: a coarse-grained molecular dynamics (CGMD) simulation study
title_short	Interaction of monomeric Ebola VP40 protein with a plasma membrane: a coarse-grained molecular dynamics (CGMD) simulation study
title_full	Interaction of monomeric Ebola VP40 protein with a plasma membrane: a coarse-grained molecular dynamics (CGMD) simulation study
title_fullStr	Interaction of monomeric Ebola VP40 protein with a plasma membrane: a coarse-grained molecular dynamics (CGMD) simulation study
title_full_unstemmed	Interaction of monomeric Ebola VP40 protein with a plasma membrane: a coarse-grained molecular dynamics (CGMD) simulation study
title_sort	interaction of monomeric ebola vp40 protein with a plasma membrane: a coarse-grained molecular dynamics (cgmd) simulation study
publisher	Elsevier
publishDate	2018
url	http://irep.iium.edu.my/63665/ http://irep.iium.edu.my/63665/ http://irep.iium.edu.my/63665/ http://irep.iium.edu.my/63665/7/63665%20Interaction%20of%20monomeric%20Ebola%20VP40%20protein%20SCOPUS.pdf http://irep.iium.edu.my/63665/13/63665_Interaction%20of%20monomeric%20Ebola%20VP40%20protein.pdf http://irep.iium.edu.my/63665/19/63665_Interaction%20of%20monomeric%20Ebola%20VP40%20protein%20with%20a%20plasma.pdf
first_indexed	2023-09-18T21:30:16Z
last_indexed	2023-09-18T21:30:16Z
_version_	1777412464213753856

Interaction of monomeric Ebola VP40 protein with a plasma membrane: a coarse-grained molecular dynamics (CGMD) simulation study

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