6soz: Difference between revisions

Latest revision as of 08:20, 17 October 2024

Glycosylated Trypanosoma brucei transferrin receptor in complex with human transferrin

Structural highlights

6soz is a 3 chain structure with sequence from Homo sapiens and Trypanosoma brucei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.42Å
Ligands:	FE, MAN, NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ESAG6_TRYBB Transferrin receptor subunit involved in receptor-mediated acquisition of iron from the environment by binding host TF/transferrin.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

To maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation(1). Within these coats are receptors for macromolecular nutrients such as transferrin(2,3). These must be accessible to their ligands but must not confer susceptibility to immunoglobulin-mediated attack. Trypanosomes have a wide host range and their receptors must also bind ligands from diverse species. To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform. The trypanosome genome contains a family of around 14 transferrin receptors(4), which has been proposed to allow binding to transferrin from different mammalian hosts(5,6). However, we find that a single receptor can bind transferrin from a broad range of mammals, indicating that receptor variation is unlikely to be necessary for promiscuity of host infection. In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.

Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion.,Trevor CE, Gonzalez-Munoz AL, Macleod OJS, Woodcock PG, Rust S, Vaughan TJ, Garman EF, Minter R, Carrington M, Higgins MK Nat Microbiol. 2019 Oct 21. pii: 10.1038/s41564-019-0589-0. doi:, 10.1038/s41564-019-0589-0. PMID:31636418^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Maier A, Steverding D. Expression and purification of non-glycosylated Trypanosoma brucei transferrin receptor in insect cells. Exp Parasitol. 2008 Oct;120(2):205-7. PMID:18680745 doi:10.1016/j.exppara.2008.07.004
↑ Trevor CE, Gonzalez-Munoz AL, Macleod OJS, Woodcock PG, Rust S, Vaughan TJ, Garman EF, Minter R, Carrington M, Higgins MK. Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion. Nat Microbiol. 2019 Oct 21. pii: 10.1038/s41564-019-0589-0. doi:, 10.1038/s41564-019-0589-0. PMID:31636418 doi:https://dx.doi.org/10.1038/s41564-019-0589-0
↑ Steverding D, Stierhof YD, Chaudhri M, Ligtenberg M, Schell D, Beck-Sickinger AG, Overath P. ESAG 6 and 7 products of Trypanosoma brucei form a transferrin binding protein complex. Eur J Cell Biol. 1994 Jun;64(1):78-87 PMID:7957316
↑ Steverding D, Stierhof YD, Fuchs H, Tauber R, Overath P. Transferrin-binding protein complex is the receptor for transferrin uptake in Trypanosoma brucei. J Cell Biol. 1995 Dec;131(5):1173-82. PMID:8522581 doi:10.1083/jcb.131.5.1173
↑ Trevor CE, Gonzalez-Munoz AL, Macleod OJS, Woodcock PG, Rust S, Vaughan TJ, Garman EF, Minter R, Carrington M, Higgins MK. Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion. Nat Microbiol. 2019 Oct 21. pii: 10.1038/s41564-019-0589-0. doi:, 10.1038/s41564-019-0589-0. PMID:31636418 doi:https://dx.doi.org/10.1038/s41564-019-0589-0

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Maier A, Steverding D. Expression and purification of non-glycosylated Trypanosoma brucei transferrin receptor in insect cells. Exp Parasitol. 2008 Oct;120(2):205-7. PMID:18680745 doi:10.1016/j.exppara.2008.07.004

[2] Trevor CE, Gonzalez-Munoz AL, Macleod OJS, Woodcock PG, Rust S, Vaughan TJ, Garman EF, Minter R, Carrington M, Higgins MK. Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion. Nat Microbiol. 2019 Oct 21. pii: 10.1038/s41564-019-0589-0. doi:, 10.1038/s41564-019-0589-0. PMID:31636418 doi:https://dx.doi.org/10.1038/s41564-019-0589-0

[3] Steverding D, Stierhof YD, Chaudhri M, Ligtenberg M, Schell D, Beck-Sickinger AG, Overath P. ESAG 6 and 7 products of Trypanosoma brucei form a transferrin binding protein complex. Eur J Cell Biol. 1994 Jun;64(1):78-87 PMID:7957316

[4] Steverding D, Stierhof YD, Fuchs H, Tauber R, Overath P. Transferrin-binding protein complex is the receptor for transferrin uptake in Trypanosoma brucei. J Cell Biol. 1995 Dec;131(5):1173-82. PMID:8522581 doi:10.1083/jcb.131.5.1173

[5] Trevor CE, Gonzalez-Munoz AL, Macleod OJS, Woodcock PG, Rust S, Vaughan TJ, Garman EF, Minter R, Carrington M, Higgins MK. Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion. Nat Microbiol. 2019 Oct 21. pii: 10.1038/s41564-019-0589-0. doi:, 10.1038/s41564-019-0589-0. PMID:31636418 doi:https://dx.doi.org/10.1038/s41564-019-0589-0

[1]

[2]

[3]

[4]

[5]

@@ Line 3: / Line 3: @@
 <StructureSection load='6soz' size='340' side='right'caption='[[6soz]], [[Resolution|resolution]] 3.42&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6soz]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SOZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SOZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6soz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SOZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SOZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.42&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6soy|6soy]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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">13J3.10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5691 Trypanosoma (Trypanozoon) brucei]), 13J3.09 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5691 Trypanosoma (Trypanozoon) brucei]), TF, PRO1400 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6soz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6soz OCA], [https://pdbe.org/6soz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6soz RCSB], [https://www.ebi.ac.uk/pdbsum/6soz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6soz ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6soz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6soz OCA], [http://pdbe.org/6soz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6soz RCSB], [http://www.ebi.ac.uk/pdbsum/6soz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6soz ProSAT]</span></td></tr>
 </table>
-== 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/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.
+[https://www.uniprot.org/uniprot/ESAG6_TRYBB ESAG6_TRYBB] Transferrin receptor subunit involved in receptor-mediated acquisition of iron from the environment by binding host TF/transferrin.<ref>PMID:18680745</ref> <ref>PMID:31636418</ref> <ref>PMID:7957316</ref> <ref>PMID:8522581</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 19: @@
 </div>
 <div class="pdbe-citations 6soz" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Transferrin 3D structures|Transferrin 3D structures]]
+*[[Transferrin receptor|Transferrin receptor]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Carrington, M]]
+[[Category: Trypanosoma brucei]]
-[[Category: Higgins, M K]]
+[[Category: Carrington M]]
-[[Category: Trevor, C]]
+[[Category: Higgins MK]]
-[[Category: Protein binding]]
+[[Category: Trevor C]]
-[[Category: Trypanosoma brucei trypanosome transferrin receptor transferrrin cell surface]]

6soz: Difference between revisions

Latest revision as of 08:20, 17 October 2024

Glycosylated Trypanosoma brucei transferrin receptor in complex with human transferrin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools