8af6c97fbdc463329eaa43b311248244 265135.pdf a78a672677bc3fb966e59c385049d4cfbd596eca 265135.pdf 75d941c52f47d972d58c28147fa7210939461592a2745f5043a6daaa781d31f3 265135.pdf Title: In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites Subject: 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 Plasmodium species and its essential role in the life cycle of Plasmodium falciparum. 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 Plasmodium chabaudi ATP2 (PcATP2), an ortholog of P. falciparum 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. Keywords: P-type ATPase; Plasmodium; flippases; coarse-grain molecular dynamics; lipid–protein fingerprinting; modelling Author: Mario López-Martín, Pedro Renault, Jesus Giraldo, José Luis Vázquez-Ibar and Alex Perálvarez-Marín Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jul 12 05:45:16 2022 CEST ModDate: Tue Jul 12 05:54:08 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3364331 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 10 0 NGHXUP+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 GIXMRN+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 YUUEFU+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 JYPLJJ+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 RNKVDG+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 KTJZVG+CMSY10 Type 1 Builtin yes yes no 70 0 CAMXTK+EURM10 Type 1 Builtin yes yes no 74 0 PCWWZT+PazoMath-Italic Type 1 Builtin yes yes no 84 0 GIGFZE+CMR10 Type 1 Builtin yes yes no 88 0 QQXUPP+PazoMath Type 1 Builtin yes yes no 92 0 JGAEPT+CMEX10 Type 1 Builtin yes yes no 99 0 EGNPFB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 109 0 EGNPFC+PalatinoLinotype CID TrueType Identity-H yes yes yes 112 0 EGNPFD+PalatinoLinotype TrueType WinAnsi yes yes no 118 0 EGNPFF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 121 0 EGNPFB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 131 0 EGNPFC+PalatinoLinotype CID TrueType Identity-H yes yes yes 134 0 EGNPFD+PalatinoLinotype TrueType WinAnsi yes yes no 140 0 EGNPFF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 143 0 EGNPFB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 153 0 EGNPFC+PalatinoLinotype CID TrueType Identity-H yes yes yes 156 0 EGNPFD+PalatinoLinotype TrueType WinAnsi yes yes no 162 0 EGNPFF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 165 0 EGNPFB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 175 0 EGNPFC+PalatinoLinotype CID TrueType Identity-H yes yes yes 178 0 EGNPFD+PalatinoLinotype TrueType WinAnsi yes yes no 184 0 EGNPFF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 187 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-06-17 02:31:51 CEST RepresentationInformation: 265135.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-06-16 14:21:27 CEST Size: 3364331 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 384 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Results and Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Info: Title: In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites Author: Mario López-Martín, Pedro Renault, Jesus Giraldo, José Luis Vázquez-Ibar and Alex Perálvarez-Marín Subject: 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 Plasmodium species and its essential role in the life cycle of Plasmodium falciparum. 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 Plasmodium chabaudi ATP2 (PcATP2), an ortholog of P. falciparum 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. Keywords: P-type ATPase; Plasmodium; flippases; coarse-grain molecular dynamics; lipid protein fingerprinting; modelling Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jul 12 05:45:16 CEST 2022 ModDate: Tue Jul 12 05:54:08 CEST 2022 ID: 0x46e104faf5d397a2537785955aba758f, 0x46e104faf5d397a2537785955aba758f Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: JGAEPT+CMEX10 FontSubset: true FirstChar: 0 LastChar: 26 FontDescriptor: FontName: JGAEPT+CMEX10 Flags: Symbolic FontBBox: -24, -2960, 1454, 772 FontFile: true Font: BaseFont: GIXMRN+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: GIXMRN+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: PCWWZT+PazoMath-Italic FontSubset: true FirstChar: 115 LastChar: 182 FontDescriptor: FontName: PCWWZT+PazoMath-Italic Flags: Symbolic FontBBox: -70, -277, 902, 733 FontFile: true Font: BaseFont: KTJZVG+CMSY10 FontSubset: true FirstChar: 0 LastChar: 54 FontDescriptor: FontName: KTJZVG+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: YUUEFU+URWPalladioL-Ital FontSubset: true FirstChar: 40 LastChar: 122 FontDescriptor: FontName: YUUEFU+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: GIGFZE+CMR10 FontSubset: true FirstChar: 40 LastChar: 61 FontDescriptor: FontName: GIGFZE+CMR10 Flags: Symbolic FontBBox: -40, -250, 1009, 750 FontFile: true Font: BaseFont: MWHIBA+VnURWPalladioL FontSubset: true FirstChar: 161 LastChar: 226 FontDescriptor: FontName: MWHIBA+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: CAMXTK+EURM10 FontSubset: true FirstChar: 12 LastChar: 22 FontDescriptor: FontName: CAMXTK+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: JYPLJJ+VnURWPalladioL-Bold FontSubset: true FirstChar: 161 LastChar: 226 FontDescriptor: FontName: JYPLJJ+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: QQXUPP+PazoMath FontSubset: true FirstChar: 229 LastChar: 229 FontDescriptor: FontName: QQXUPP+PazoMath Flags: Symbolic FontBBox: -40, -283, 878, 946 FontFile: true Font: BaseFont: NGHXUP+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 150 FontDescriptor: FontName: NGHXUP+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 34, 335, 152, 344 Annotation: Subtype: Link Rect: 34, 325, 100, 332 Annotation: Subtype: Link Rect: 34, 164, 96, 186 Annotation: Subtype: Link Rect: 126, 90, 154, 99 Annotation: Subtype: Link Rect: 34, 78, 147, 87 Annotation: Subtype: Link Rect: 34, 756, 166, 792 Annotation: Subtype: Link Rect: 515, 756, 560, 792 Annotation: Subtype: Link Rect: 140, 662, 151, 676 Annotation: Subtype: Link Rect: 340, 662, 351, 676 Annotation: Subtype: Link Rect: 177, 652, 188, 663 Annotation: Subtype: Link Rect: 393, 184, 400, 193 ActionDest: 194 Annotation: Subtype: Link Rect: 272, 159, 279, 167 ActionDest: 194 Annotation: Subtype: Link Rect: 298, 133, 305, 142 ActionDest: 194 Annotation: Subtype: Link Rect: 306, 83, 313, 92 ActionDest: 194 Annotation: Subtype: Link Rect: 122, 17, 288, 28 Annotation: Subtype: Link Rect: 395, 17, 560, 28 Annotation: Subtype: Link Rect: 34, 432, 87, 451 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 519, 735, 526, 744 ActionDest: 194 Annotation: Subtype: Link Rect: 379, 698, 386, 707 ActionDest: 194 Annotation: Subtype: Link Rect: 251, 660, 258, 669 ActionDest: 194 Annotation: Subtype: Link Rect: 454, 610, 461, 619 ActionDest: 194 Annotation: Subtype: Link Rect: 549, 396, 556, 405 ActionDest: 194 Annotation: Subtype: Link Rect: 508, 384, 515, 393 ActionDest: 194 Annotation: Subtype: Link Rect: 522, 371, 529, 380 ActionDest: 194 Annotation: Subtype: Link Rect: 209, 333, 221, 342 ActionDest: 194 Annotation: Subtype: Link Rect: 382, 321, 394, 330 ActionDest: 194 Annotation: Subtype: Link Rect: 461, 308, 468, 317 ActionDest: 194 Annotation: Subtype: Link Rect: 471, 258, 483, 267 ActionDest: 194 Annotation: Subtype: Link Rect: 484, 258, 496, 267 ActionDest: 194 Annotation: Subtype: Link Rect: 199, 233, 211, 242 ActionDest: 194 Annotation: Subtype: Link Rect: 212, 233, 224, 242 ActionDest: 194 Annotation: Subtype: Link Rect: 486, 193, 493, 205 ActionDest: 78 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 302, 455, 314, 464 ActionDest: 194 Annotation: Subtype: Link Rect: 207, 367, 219, 376 ActionDest: 194 Annotation: Subtype: Link Rect: 220, 368, 232, 376 ActionDest: 194 Annotation: Subtype: Link Rect: 188, 179, 200, 188 ActionDest: 194 Annotation: Subtype: Link Rect: 381, 166, 393, 176 ActionDest: 194 Annotation: Subtype: Link Rect: 253, 154, 265, 163 ActionDest: 194 Annotation: Subtype: Link Rect: 532, 141, 544, 150 ActionDest: 198 Annotation: Subtype: Link Rect: 545, 141, 556, 150 ActionDest: 198 Annotation: Subtype: Link Rect: 522, 116, 534, 125 ActionDest: 198 Annotation: Subtype: Link Rect: 344, 79, 356, 88 ActionDest: 198 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 204, 710, 216, 719 ActionDest: 198 Annotation: Subtype: Link Rect: 219, 710, 231, 719 ActionDest: 198 Annotation: Subtype: Link Rect: 423, 553, 435, 562 ActionDest: 198 Annotation: Subtype: Link Rect: 436, 553, 448, 562 ActionDest: 198 Annotation: Subtype: Link Rect: 331, 515, 338, 524 ActionDest: 194 Annotation: Subtype: Link Rect: 367, 465, 379, 474 ActionDest: 198 Annotation: Subtype: Link Rect: 380, 465, 392, 474 ActionDest: 198 Annotation: Subtype: Link Rect: 209, 359, 221, 368 ActionDest: 198 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 339, 660, 351, 669 ActionDest: 198 Annotation: Subtype: Link Rect: 532, 376, 544, 385 ActionDest: 198 Annotation: Subtype: Link Rect: 544, 376, 556, 385 ActionDest: 198 Annotation: Subtype: Link Rect: 477, 326, 489, 335 ActionDest: 198 Annotation: Subtype: Link Rect: 490, 326, 502, 335 ActionDest: 198 Annotation: Subtype: Link Rect: 430, 313, 442, 322 ActionDest: 198 Annotation: Subtype: Link Rect: 199, 238, 211, 247 ActionDest: 198 Annotation: Subtype: Link Rect: 226, 162, 238, 171 ActionDest: 198 Annotation: Subtype: Link Rect: 238, 162, 250, 171 ActionDest: 198 Annotation: Subtype: Link Rect: 544, 112, 556, 121 ActionDest: 198 Annotation: Subtype: Link Rect: 455, 87, 467, 96 ActionDest: 198 Annotation: Subtype: Link Rect: 467, 87, 479, 96 ActionDest: 198 Annotation: Subtype: Link Rect: 533, 62, 545, 71 ActionDest: 198 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 217, 733, 224, 745 ActionDest: 103 Annotation: Subtype: Link Rect: 275, 733, 282, 745 ActionDest: 78 Annotation: Subtype: Link Rect: 253, 660, 260, 669 ActionDest: 194 Annotation: Subtype: Link Rect: 419, 648, 426, 657 ActionDest: 194 Annotation: Subtype: Link Rect: 232, 297, 243, 305 ActionDest: 198 Annotation: Subtype: Link Rect: 219, 170, 226, 182 ActionDest: 103 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 273, 695, 280, 707 ActionDest: 125 Annotation: Subtype: Link Rect: 233, 352, 245, 361 ActionDest: 198 Annotation: Subtype: Link Rect: 245, 352, 257, 361 ActionDest: 198 Annotation: Subtype: Link Rect: 260, 352, 272, 361 ActionDest: 198 Annotation: Subtype: Link Rect: 513, 314, 525, 323 ActionDest: 198 Annotation: Subtype: Link Rect: 204, 214, 216, 223 ActionDest: 198 Annotation: Subtype: Link Rect: 516, 214, 523, 223 ActionDest: 194 Annotation: Subtype: Link Rect: 423, 189, 435, 198 ActionDest: 198 Annotation: Subtype: Link Rect: 436, 189, 448, 198 ActionDest: 198 Annotation: Subtype: Link Rect: 448, 189, 460, 198 ActionDest: 198 Annotation: Subtype: Link Rect: 252, 113, 264, 122 ActionDest: 198 Annotation: Subtype: Link Rect: 548, 101, 555, 110 ActionDest: 194 Annotation: Subtype: Link Rect: 198, 76, 210, 85 ActionDest: 201 Annotation: Subtype: Link Rect: 210, 76, 222, 85 ActionDest: 201 Annotation: Subtype: Link Rect: 477, 63, 489, 72 ActionDest: 198 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 237, 723, 249, 732 ActionDest: 201 Annotation: Subtype: Link Rect: 343, 698, 354, 707 ActionDest: 198 Annotation: Subtype: Link Rect: 355, 698, 367, 707 ActionDest: 201 Annotation: Subtype: Link Rect: 443, 685, 450, 694 ActionDest: 194 Annotation: Subtype: Link Rect: 299, 647, 311, 657 ActionDest: 198 Annotation: Subtype: Link Rect: 456, 620, 463, 632 ActionDest: 147 Annotation: Subtype: Link Rect: 547, 519, 554, 531 ActionDest: 147 Annotation: Subtype: Link Rect: 241, 510, 248, 519 ActionDest: 194 Annotation: Subtype: Link Rect: 475, 102, 482, 114 ActionDest: 169 Annotation: Subtype: Link Rect: 368, 92, 380, 101 ActionDest: 198 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 384, 733, 391, 745 ActionDest: 169 Annotation: Subtype: Link Rect: 430, 695, 437, 707 ActionDest: 169 Annotation: Subtype: Link Rect: 339, 622, 351, 631 ActionDest: 198 Annotation: Subtype: Link Rect: 221, 126, 233, 135 ActionDest: 198 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 544, 723, 556, 732 ActionDest: 198 Annotation: Subtype: Link Rect: 356, 685, 368, 694 ActionDest: 198 Annotation: Subtype: Link Rect: 475, 622, 487, 631 ActionDest: 201 Annotation: Subtype: Link Rect: 352, 547, 364, 556 ActionDest: 198 Annotation: Subtype: Link Rect: 284, 447, 296, 456 ActionDest: 201 Annotation: Subtype: Link Rect: 329, 233, 341, 242 ActionDest: 201 Annotation: Subtype: Link Rect: 525, 169, 560, 180 Annotation: Subtype: Link Rect: 165, 157, 394, 168 Annotation: Subtype: Link Rect: 520, 75, 531, 84 ActionDest: 201 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 160, 501, 197, 512 Annotation: Subtype: Link Rect: 469, 478, 507, 489 Annotation: Subtype: Link Rect: 457, 466, 495, 477 Annotation: Subtype: Link Rect: 350, 443, 387, 454 Annotation: Subtype: Link Rect: 254, 420, 291, 431 Annotation: Subtype: Link Rect: 164, 386, 202, 396 Annotation: Subtype: Link Rect: 265, 351, 302, 362 Annotation: Subtype: Link Rect: 340, 328, 378, 339 Annotation: Subtype: Link Rect: 113, 306, 151, 316 Annotation: Subtype: Link Rect: 389, 282, 427, 293 Annotation: Subtype: Link Rect: 287, 260, 324, 270 Annotation: Subtype: Link Rect: 516, 236, 553, 247 Annotation: Subtype: Link Rect: 447, 213, 485, 224 Annotation: Subtype: Link Rect: 104, 191, 141, 201 Annotation: Subtype: Link Rect: 351, 167, 389, 178 Annotation: Subtype: Link Rect: 313, 132, 350, 143 Annotation: Subtype: Link Rect: 104, 99, 142, 109 Annotation: Subtype: Link Rect: 166, 76, 203, 86 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 259, 722, 297, 733 Annotation: Subtype: Link Rect: 59, 653, 96, 664 Annotation: Subtype: Link Rect: 314, 630, 352, 640 Annotation: Subtype: Link Rect: 358, 630, 394, 640 Annotation: Subtype: Link Rect: 245, 607, 283, 617 Annotation: Subtype: Link Rect: 289, 607, 325, 617 Annotation: Subtype: Link Rect: 398, 583, 435, 594 Annotation: Subtype: Link Rect: 442, 583, 478, 594 Annotation: Subtype: Link Rect: 441, 560, 479, 571 Annotation: Subtype: Link Rect: 262, 537, 299, 548 Annotation: Subtype: Link Rect: 320, 514, 358, 525 Annotation: Subtype: Link Rect: 104, 481, 141, 491 Annotation: Subtype: Link Rect: 156, 457, 193, 468 Annotation: Subtype: Link Rect: 496, 434, 534, 445 Annotation: Subtype: Link Rect: 432, 411, 470, 422 Annotation: Subtype: Link Rect: 399, 399, 437, 410 Annotation: Subtype: Link Rect: 407, 388, 445, 399 Annotation: Subtype: Link Rect: 431, 365, 469, 376 Annotation: Subtype: Link Rect: 475, 365, 511, 376 Annotation: Subtype: Link Rect: 291, 342, 329, 353 Annotation: Subtype: Link Rect: 335, 342, 371, 353 Annotation: Subtype: Link Rect: 290, 307, 328, 318 Annotation: Subtype: Link Rect: 365, 284, 403, 295 Annotation: Subtype: Link Rect: 409, 284, 445, 295 Annotation: Subtype: Link Rect: 342, 261, 380, 272 Annotation: Subtype: Link Rect: 322, 238, 360, 249 Annotation: Subtype: Link Rect: 441, 215, 479, 226 Annotation: Subtype: Link Rect: 485, 215, 521, 226 Annotation: Subtype: Link Rect: 186, 192, 223, 203 Annotation: Subtype: Link Rect: 353, 169, 391, 180 Annotation: Subtype: Link Rect: 487, 146, 524, 157 Annotation: Subtype: Link Rect: 59, 124, 96, 134 Annotation: Subtype: Link Rect: 102, 124, 138, 134 Annotation: Subtype: Link Rect: 59, 101, 96, 111 Annotation: Subtype: Link Rect: 102, 101, 138, 111 Annotation: Subtype: Link Rect: 122, 78, 160, 88 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 241, 722, 279, 733 Annotation: Subtype: Link Rect: 179, 688, 217, 698 Annotation: Subtype: Link Rect: 409, 664, 446, 675 Annotation: Subtype: Link Rect: 238, 641, 275, 652 Annotation: Subtype: Link Rect: 311, 618, 348, 629 Annotation: Subtype: Link Rect: 228, 595, 265, 606 Annotation: Subtype: Link Rect: 271, 595, 307, 606 Annotation: Subtype: Link Rect: 201, 572, 238, 583 Annotation: Subtype: Link Rect: 245, 572, 281, 583 Annotation: Subtype: Link Rect: 113, 550, 150, 560 Checksum: ff3cb2ae Type: CRC32 Checksum: 8af6c97fbdc463329eaa43b311248244 Type: MD5 Checksum: a78a672677bc3fb966e59c385049d4cfbd596eca Type: SHA-1