View source for 6d04


==Cryo-EM structure of a Plasmodium vivax invasion complex essential for entry into human reticulocytes; two molecules of parasite ligand, subclass 1.==
<SX load='6d04' size='340' side='right' viewer='molstar' caption='[[6d04]], [[Resolution|resolution]] 3.74&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6d04]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human], [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Plavs Plavs]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D04 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6D04 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TFRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PVX_094255 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=126793 PLAVS])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6d04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d04 OCA], [http://pdbe.org/6d04 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d04 RCSB], [http://www.ebi.ac.uk/pdbsum/6d04 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d04 ProSAT]</span></td></tr>
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== Disease ==
[[http://www.uniprot.org/uniprot/TRFE_HUMAN TRFE_HUMAN]] Defects in TF are the cause of atransferrinemia (ATRAF) [MIM:[http://omim.org/entry/209300 209300]]. Atransferrinemia is rare autosomal recessive disorder characterized by iron overload and hypochromic anemia.<ref>PMID:11110675</ref> <ref>PMID:15466165</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/TFR1_HUMAN TFR1_HUMAN]] Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the heditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site.<ref>PMID:3568132</ref>  [[http://www.uniprot.org/uniprot/TRFE_HUMAN TRFE_HUMAN]] Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation. 
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== Publication Abstract from PubMed ==
Plasmodium vivax is the most widely distributed malaria parasite that infects humans(1). P. vivax invades reticulocytes exclusively, and successful entry depends on specific interactions between the P. vivax reticulocyte-binding protein 2b (PvRBP2b) and transferrin receptor 1 (TfR1)(2). TfR1-deficient erythroid cells are refractory to invasion by P. vivax, and anti-PvRBP2b monoclonal antibodies inhibit reticulocyte binding and block P. vivax invasion in field isolates(2). Here we report a high-resolution cryo-electron microscopy structure of a ternary complex of PvRBP2b bound to human TfR1 and transferrin, at 3.7 A resolution. Mutational analyses show that PvRBP2b residues involved in complex formation are conserved; this suggests that antigens could be designed that act across P. vivax strains. Functional analyses of TfR1 highlight how P. vivax hijacks TfR1, an essential housekeeping protein, by binding to sites that govern host specificity, without affecting its cellular function of transporting iron. Crystal and solution structures of PvRBP2b in complex with antibody fragments characterize the inhibitory epitopes. Our results establish a structural framework for understanding how P. vivax reticulocyte-binding protein engages its receptor and the molecular mechanism of inhibitory monoclonal antibodies, providing important information for the design of novel vaccine candidates.

Cryo-EM structure of an essential Plasmodium vivax invasion complex.,Gruszczyk J, Huang RK, Chan LJ, Menant S, Hong C, Murphy JM, Mok YF, Griffin MDW, Pearson RD, Wong W, Cowman AF, Yu Z, Tham WH Nature. 2018 Jul;559(7712):135-139. doi: 10.1038/s41586-018-0249-1. Epub 2018 Jun, 27. PMID:29950717<ref>PMID:29950717</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6d04" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transferrin 3D structures|Transferrin 3D structures]]
*[[Transferrin receptor|Transferrin receptor]]
== References ==
<references/>
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</SX>
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Plavs]]
[[Category: Gruszczyk, J]]
[[Category: Hong, C]]
[[Category: Huang, R K]]
[[Category: Tham, W H]]
[[Category: Yu, Z]]
[[Category: Cell invasion]]
[[Category: Invasion]]
[[Category: Malaria]]
[[Category: Plasmodium vivax]]
[[Category: Reticulocyte]]