3fru
From Proteopedia
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- | [[Image:3fru.png|left|200px]] | ||
- | + | ==NEONATAL FC RECEPTOR, PH 6.5== | |
+ | <StructureSection load='3fru' size='340' side='right'caption='[[3fru]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
+ | == Structural highlights == | ||
+ | <table><tr><td colspan='2'>[[3fru]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FRU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FRU FirstGlance]. <br> | ||
+ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | ||
+ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=3fru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fru OCA], [https://pdbe.org/3fru PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fru RCSB], [https://www.ebi.ac.uk/pdbsum/3fru PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fru ProSAT]</span></td></tr> | ||
+ | </table> | ||
+ | == Function == | ||
+ | [https://www.uniprot.org/uniprot/FCGRN_RAT FCGRN_RAT] Binds to the Fc region of monomeric immunoglobulins gamma. Mediates the selective uptake of IgG from milk and helps newborn animals to acquire passive immunity. IgG in the milk is bound at the apical surface of the intestinal epithelium. The resultant FcRn-IgG complexes are transcytosed across the intestinal epithelium and IgG is released from FcRn into blood or tissue fluids (By similarity). | ||
+ | == Evolutionary Conservation == | ||
+ | [[Image:Consurf_key_small.gif|200px|right]] | ||
+ | Check<jmol> | ||
+ | <jmolCheckbox> | ||
+ | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fr/3fru_consurf.spt"</scriptWhenChecked> | ||
+ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
+ | <text>to colour the structure by Evolutionary Conservation</text> | ||
+ | </jmolCheckbox> | ||
+ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3fru ConSurf]. | ||
+ | <div style="clear:both"></div> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | BACKGROUND: The neonatal Fc receptor (FcRn) mediates the transcytosis of maternal immunoglobulin G (IgG) across fetal and/or neonatal tissues for the acquisition of passive immunity. In adults, FcRn is involved in the maintenance of high serum IgG levels. Both processes are mediated by pH-dependent IgG binding to FcRn-FcRn binds to IgG with nanomolar affinity at pH 6, but shows no detectable binding at pH 7.5. At pH 6, FcRn is more thermally stable and the dissociation rate of its light chain is an order of magnitude slower than at pH 8.0. Comparison of the structures of FcRn at pH 6.5 and pH 8 allows an analysis of the structural basis for the receptor's pH-dependent ligand binding and stability. RESULTS: We have determined the structure of FcRn at pH 8 and compared it to a further refined version of the structure at pH 6.5. An extensive ordered carbohydrate structure is observed at both pH values. The two structures are very similar; thus the pH dependence of FcRn stability and affinity for IgG can be attributed to chemical properties of the structures themselves, rather than mechanisms that rely on conformational changes. The pH-dependent properties are mediated by electrostatic interactions involving histidine residues, which are more favorable for the protonated form of histidine that predominates at acidic pH values. CONCLUSIONS: No major conformational change is observed between the pH 6.5 and pH 8 structures of FcRn that could account for the differences in affinity for IgG. The pH dependence of IgG binding to FcRn can therefore primarily be attributed to titration of histidine residues on Fc that interact with anionic pockets on the receptor. The FcRn dimer, which is required for high affinity binding of IgG, is itself stabilized at acidic pH by histidine-mediated salt bridges and a sidechain rearrangement that creates a more favorable interaction with an anionic pocket at pH 6.5 relative to pH 8. FcRn dimerization is facilitated by reciprocal interactions in which carbohydrate from one receptor molecule binds to protein residues from the dimer-related receptor molecule to form a 'carbohydrate handshake'. | ||
- | + | Structural basis of pH-dependent antibody binding by the neonatal Fc receptor.,Vaughn DE, Bjorkman PJ Structure. 1998 Jan 15;6(1):63-73. PMID:9493268<ref>PMID:9493268</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | + | </div> | |
- | + | <div class="pdbe-citations 3fru" style="background-color:#fffaf0;"></div> | |
- | + | ||
==See Also== | ==See Also== | ||
- | *[[Beta-2 microglobulin|Beta-2 microglobulin]] | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
- | + | == References == | |
- | == | + | <references/> |
- | < | + | __TOC__ |
+ | </StructureSection> | ||
+ | [[Category: Large Structures]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
- | [[Category: Bjorkman | + | [[Category: Bjorkman PJ]] |
- | [[Category: Burmeister | + | [[Category: Burmeister WP]] |
- | [[Category: Vaughn | + | [[Category: Vaughn DE]] |
Current revision
NEONATAL FC RECEPTOR, PH 6.5
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