In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites
ATP2, a putative type 4 P-type ATPase, is a phosphatidylinositol-4-phosphate (PI4P)-regulated phospholipid transporter with an interesting potential as an antimalarial drug target due to its conservation across <i>Plasmodium</i> species and its essential role in the life cycle of <i&g...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Membranes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0375/12/7/702 |
| _version_ | 1827605097951002624 |
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| author | Mario López-Martín Pedro Renault Jesus Giraldo José Luis Vázquez-Ibar Alex Perálvarez-Marín |
| author_facet | Mario López-Martín Pedro Renault Jesus Giraldo José Luis Vázquez-Ibar Alex Perálvarez-Marín |
| author_sort | Mario López-Martín |
| collection | DOAJ |
| description | ATP2, a putative type 4 P-type ATPase, is a phosphatidylinositol-4-phosphate (PI4P)-regulated phospholipid transporter with an interesting potential as an antimalarial drug target due to its conservation across <i>Plasmodium</i> species and its essential role in the life cycle of <i>Plasmodium falciparum</i>. Despite its importance, the exact mechanism of its action and regulation is still not fully understood. In this study we used coarse-grained molecular dynamics (CG-MD) to elucidate the lipid–protein interactions between a heterogeneous lipid membrane containing phosphatidylinositol and <i>Plasmodium chabaudi</i> ATP2 (PcATP2), an ortholog of <i>P. falciparum</i> ATP2. Our study reveals structural information of the lipid fingerprint of ATP2, and provides structural information on the potential phosphatidylinositol allosteric binding site. Moreover, we identified a set of evolutionary conserved residues that may play a key role in the binding and stabilization of lipids in the binding pocket. |
| first_indexed | 2024-03-09T06:13:53Z |
| format | Article |
| id | doaj.art-9f228b80e99341358a2590673bc013c3 |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-09T06:13:53Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj.art-9f228b80e99341358a2590673bc013c32023-12-03T11:55:32ZengMDPI AGMembranes2077-03752022-07-0112770210.3390/membranes12070702In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria ParasitesMario López-Martín0Pedro Renault1Jesus Giraldo2José Luis Vázquez-Ibar3Alex Perálvarez-Marín4Biophysics Unit, Department of Biochemistry and Molecular Biology, School of Medicine, Universitat Autònoma de Barcelona, 08193 Bellaterra, SpainInstitut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, SpainInstitut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, SpainInstitute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, 91198 Gif-sur-Yvette, FranceBiophysics Unit, Department of Biochemistry and Molecular Biology, School of Medicine, Universitat Autònoma de Barcelona, 08193 Bellaterra, SpainATP2, a putative type 4 P-type ATPase, is a phosphatidylinositol-4-phosphate (PI4P)-regulated phospholipid transporter with an interesting potential as an antimalarial drug target due to its conservation across <i>Plasmodium</i> species and its essential role in the life cycle of <i>Plasmodium falciparum</i>. Despite its importance, the exact mechanism of its action and regulation is still not fully understood. In this study we used coarse-grained molecular dynamics (CG-MD) to elucidate the lipid–protein interactions between a heterogeneous lipid membrane containing phosphatidylinositol and <i>Plasmodium chabaudi</i> ATP2 (PcATP2), an ortholog of <i>P. falciparum</i> ATP2. Our study reveals structural information of the lipid fingerprint of ATP2, and provides structural information on the potential phosphatidylinositol allosteric binding site. Moreover, we identified a set of evolutionary conserved residues that may play a key role in the binding and stabilization of lipids in the binding pocket.https://www.mdpi.com/2077-0375/12/7/702P-type ATPase<i>Plasmodium</i>flippasescoarse-grain molecular dynamicslipid–protein fingerprintingmodelling |
| spellingShingle | Mario López-Martín Pedro Renault Jesus Giraldo José Luis Vázquez-Ibar Alex Perálvarez-Marín In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites Membranes P-type ATPase <i>Plasmodium</i> flippases coarse-grain molecular dynamics lipid–protein fingerprinting modelling |
| title | In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites |
| title_full | In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites |
| title_fullStr | In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites |
| title_full_unstemmed | In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites |
| title_short | In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites |
| title_sort | in silico assessment of the lipid fingerprint signature of atp2 the essential p4 atpase of malaria parasites |
| topic | P-type ATPase <i>Plasmodium</i> flippases coarse-grain molecular dynamics lipid–protein fingerprinting modelling |
| url | https://www.mdpi.com/2077-0375/12/7/702 |
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