Structural analysis of P. falciparum KAHRP and PfEMP1 complexes with host erythrocyte spectrin suggests a model for cytoadherent knob protrusions.
Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) and Knob-associated Histidine-rich Protein (KAHRP) are directly linked to malaria pathology. PfEMP1 and KAHRP cluster on protrusions (knobs) on the P. falciparum-infected erythrocyte surface and enable pathogenic cytoadherence of infected...
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Public Library of Science (PLoS)
2017-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006552&type=printable |
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| author | Erin E Cutts Niklas Laasch Dirk M Reiter Raphael Trenker Leanne M Slater Phillip J Stansfeld Ioannis Vakonakis |
| author_facet | Erin E Cutts Niklas Laasch Dirk M Reiter Raphael Trenker Leanne M Slater Phillip J Stansfeld Ioannis Vakonakis |
| author_sort | Erin E Cutts |
| collection | DOAJ |
| description | Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) and Knob-associated Histidine-rich Protein (KAHRP) are directly linked to malaria pathology. PfEMP1 and KAHRP cluster on protrusions (knobs) on the P. falciparum-infected erythrocyte surface and enable pathogenic cytoadherence of infected erythrocytes to the host microvasculature, leading to restricted blood flow, oxygen deprivation and damage of tissues. Here we characterize the interactions of PfEMP1 and KAHRP with host erythrocyte spectrin using biophysical, structural and computational approaches. These interactions assist knob formation and, thus, promote cytoadherence. We show that the folded core of the PfEMP1 cytosolic domain interacts broadly with erythrocyte spectrin but shows weak, residue-specific preference for domain 17 of α spectrin, which is proximal to the erythrocyte cytoskeletal junction. In contrast, a protein sequence repeat region in KAHRP preferentially associates with domains 10-14 of β spectrin, proximal to the spectrin-ankyrin complex. Structural models of PfEMP1 and KAHRP with spectrin combined with previous microscopy and protein interaction data suggest a model for knob architecture. |
| format | Article |
| id | doaj-art-97e05a91c1c54289b5b586d310981f6f |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2017-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-97e05a91c1c54289b5b586d310981f6f2025-08-20T03:12:47ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742017-08-01138e100655210.1371/journal.ppat.1006552Structural analysis of P. falciparum KAHRP and PfEMP1 complexes with host erythrocyte spectrin suggests a model for cytoadherent knob protrusions.Erin E CuttsNiklas LaaschDirk M ReiterRaphael TrenkerLeanne M SlaterPhillip J StansfeldIoannis VakonakisPlasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) and Knob-associated Histidine-rich Protein (KAHRP) are directly linked to malaria pathology. PfEMP1 and KAHRP cluster on protrusions (knobs) on the P. falciparum-infected erythrocyte surface and enable pathogenic cytoadherence of infected erythrocytes to the host microvasculature, leading to restricted blood flow, oxygen deprivation and damage of tissues. Here we characterize the interactions of PfEMP1 and KAHRP with host erythrocyte spectrin using biophysical, structural and computational approaches. These interactions assist knob formation and, thus, promote cytoadherence. We show that the folded core of the PfEMP1 cytosolic domain interacts broadly with erythrocyte spectrin but shows weak, residue-specific preference for domain 17 of α spectrin, which is proximal to the erythrocyte cytoskeletal junction. In contrast, a protein sequence repeat region in KAHRP preferentially associates with domains 10-14 of β spectrin, proximal to the spectrin-ankyrin complex. Structural models of PfEMP1 and KAHRP with spectrin combined with previous microscopy and protein interaction data suggest a model for knob architecture.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006552&type=printable |
| spellingShingle | Erin E Cutts Niklas Laasch Dirk M Reiter Raphael Trenker Leanne M Slater Phillip J Stansfeld Ioannis Vakonakis Structural analysis of P. falciparum KAHRP and PfEMP1 complexes with host erythrocyte spectrin suggests a model for cytoadherent knob protrusions. PLoS Pathogens |
| title | Structural analysis of P. falciparum KAHRP and PfEMP1 complexes with host erythrocyte spectrin suggests a model for cytoadherent knob protrusions. |
| title_full | Structural analysis of P. falciparum KAHRP and PfEMP1 complexes with host erythrocyte spectrin suggests a model for cytoadherent knob protrusions. |
| title_fullStr | Structural analysis of P. falciparum KAHRP and PfEMP1 complexes with host erythrocyte spectrin suggests a model for cytoadherent knob protrusions. |
| title_full_unstemmed | Structural analysis of P. falciparum KAHRP and PfEMP1 complexes with host erythrocyte spectrin suggests a model for cytoadherent knob protrusions. |
| title_short | Structural analysis of P. falciparum KAHRP and PfEMP1 complexes with host erythrocyte spectrin suggests a model for cytoadherent knob protrusions. |
| title_sort | structural analysis of p falciparum kahrp and pfemp1 complexes with host erythrocyte spectrin suggests a model for cytoadherent knob protrusions |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006552&type=printable |
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