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| | <StructureSection load='6rq7' size='340' side='right'caption='[[6rq7]], [[Resolution|resolution]] 2.69Å' scene=''> | | <StructureSection load='6rq7' size='340' side='right'caption='[[6rq7]], [[Resolution|resolution]] 2.69Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6rq7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RQ7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RQ7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rq7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RQ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RQ7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DO3:10-((2R)-2-HYDROXYPROPYL)-1,4,7,10-TETRAAZACYCLODODECANE+1,4,7-TRIACETIC+ACID'>DO3</scene>, <scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</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]] 2.69Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5okl|5okl]], [[6fak|6fak]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DO3:10-((2R)-2-HYDROXYPROPYL)-1,4,7,10-TETRAAZACYCLODODECANE+1,4,7-TRIACETIC+ACID'>DO3</scene>, <scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</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">AFM, ALB2, ALBA ([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=6rq7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rq7 OCA], [https://pdbe.org/6rq7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rq7 RCSB], [https://www.ebi.ac.uk/pdbsum/6rq7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rq7 ProSAT]</span></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=6rq7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rq7 OCA], [http://pdbe.org/6rq7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rq7 RCSB], [http://www.ebi.ac.uk/pdbsum/6rq7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rq7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AFAM_HUMAN AFAM_HUMAN]] Vitamin E binding protein. May transport vitamin E in body fluids under conditions where the lipoprotein system is not sufficient. May be involved in the regulation and transport of vitamin E at the blood-brain barrier.<ref>PMID:12463752</ref> <ref>PMID:15952736</ref> <ref>PMID:19046407</ref> | + | [https://www.uniprot.org/uniprot/AFAM_HUMAN AFAM_HUMAN] Vitamin E binding protein. May transport vitamin E in body fluids under conditions where the lipoprotein system is not sufficient. May be involved in the regulation and transport of vitamin E at the blood-brain barrier.<ref>PMID:12463752</ref> <ref>PMID:15952736</ref> <ref>PMID:19046407</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Afamin, which is a human blood plasma glycoprotein, a putative multifunctional transporter of hydrophobic molecules and a marker for metabolic syndrome, poses multiple challenges for crystallographic structure determination, both practically and in analysis of the models. Several hundred crystals were analysed, and an unusual variability in cell volume and difficulty in solving the structure despite an approximately 34% sequence identity with nonglycosylated human serum albumin indicated that the molecule exhibits variable and context-sensitive packing, despite the simplified glycosylation in insect cell-expressed recombinant afamin. Controlled dehydration of the crystals was able to stabilize the orthorhombic crystal form, reducing the number of molecules in the asymmetric unit from the monoclinic form and changing the conformational state of the protein. An iterative strategy using fully automatic experiments available on MASSIF-1 was used to quickly determine the optimal protocol to achieve the phase transition, which should be readily applicable to many types of sample. The study also highlights the drawback of using a single crystallographic structure model for computational modelling purposes given that the conformational state of the binding sites and the electron density in the binding site, which is likely to result from PEGs, greatly varies between models. This also holds for the analysis of nonspecific low-affinity ligands, where often a variety of fragments with similar uncertainty can be modelled, inviting interpretative bias. As a promiscuous transporter, afamin also seems to bind gadoteridol, a magnetic resonance imaging contrast compound, in at least two sites. One pair of gadoteridol molecules is located near the human albumin Sudlow site, and a second gadoteridol molecule is located at an intermolecular site in proximity to domain IA. The data from the co-crystals support modern metrics of data quality in the context of the information that can be gleaned from data sets that would be abandoned on classical measures.
| + | |
| - | | + | |
| - | Controlled dehydration, structural flexibility and gadolinium MRI contrast compound binding in the human plasma glycoprotein afamin.,Naschberger A, Juyoux P, von Velsen J, Rupp B, Bowler MW Acta Crystallogr D Struct Biol. 2019 Dec 1;75(Pt 12):1071-1083. doi:, 10.1107/S2059798319013500. Epub 2019 Nov 19. PMID:31793901<ref>PMID:31793901</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6rq7" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bowler, M W]] | + | [[Category: Bowler MW]] |
| - | [[Category: Juyoux, P]] | + | [[Category: Juyoux P]] |
| - | [[Category: Naschberger, A]] | + | [[Category: Naschberger A]] |
| - | [[Category: Rupp, B]] | + | [[Category: Rupp B]] |
| - | [[Category: VonVelsen, J]] | + | [[Category: VonVelsen J]] |
| - | [[Category: Afamin]]
| + | |
| - | [[Category: Conformational variability]]
| + | |
| - | [[Category: Gadoteridol]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hydrophobic ligand]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| - | [[Category: Wnt-signalling]]
| + | |
| Structural highlights
Function
AFAM_HUMAN Vitamin E binding protein. May transport vitamin E in body fluids under conditions where the lipoprotein system is not sufficient. May be involved in the regulation and transport of vitamin E at the blood-brain barrier.[1] [2] [3]
References
- ↑ Voegele AF, Jerkovic L, Wellenzohn B, Eller P, Kronenberg F, Liedl KR, Dieplinger H. Characterization of the vitamin E-binding properties of human plasma afamin. Biochemistry. 2002 Dec 10;41(49):14532-8. PMID:12463752
- ↑ Jerkovic L, Voegele AF, Chwatal S, Kronenberg F, Radcliffe CM, Wormald MR, Lobentanz EM, Ezeh B, Eller P, Dejori N, Dieplinger B, Lottspeich F, Sattler W, Uhr M, Mechtler K, Dwek RA, Rudd PM, Baier G, Dieplinger H. Afamin is a novel human vitamin E-binding glycoprotein characterization and in vitro expression. J Proteome Res. 2005 May-Jun;4(3):889-99. doi: 10.1021/pr0500105. PMID:15952736 doi:http://dx.doi.org/10.1021/pr0500105
- ↑ Kratzer I, Bernhart E, Wintersperger A, Hammer A, Waltl S, Malle E, Sperk G, Wietzorrek G, Dieplinger H, Sattler W. Afamin is synthesized by cerebrovascular endothelial cells and mediates alpha-tocopherol transport across an in vitro model of the blood-brain barrier. J Neurochem. 2009 Feb;108(3):707-18. doi: 10.1111/j.1471-4159.2008.05796.x. Epub , 2008 Nov 27. PMID:19046407 doi:http://dx.doi.org/10.1111/j.1471-4159.2008.05796.x
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