View source for 6c98


==Crystal structure of FcRn bound to UCB-84==
<StructureSection load='6c98' size='340' side='right'caption='[[6c98]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6c98]] is a 4 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=6C98 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C98 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]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=ER7:1-[7-(3-fluorophenyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]ethanone'>ER7</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=6c98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c98 OCA], [https://pdbe.org/6c98 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c98 RCSB], [https://www.ebi.ac.uk/pdbsum/6c98 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c98 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FCGRN_HUMAN FCGRN_HUMAN] Binds to the Fc region of monomeric immunoglobulins gamma. Mediates the uptake of IgG from milk. Possible role in transfer of immunoglobulin G from mother to fetus.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Aiming at the design of an allosteric modulator of the neonatal Fc receptor (FcRn)-Immunoglobulin G (IgG) interaction, we developed a new methodology including NMR fragment screening, X-ray crystallography, and magic-angle-spinning (MAS) NMR at 100 kHz after sedimentation, exploiting very fast spinning of the nondeuterated soluble 42 kDa receptor construct to obtain resolved proton-detected 2D and 3D NMR spectra. FcRn plays a crucial role in regulation of IgG and serum albumin catabolism. It is a clinically validated drug target for the treatment of autoimmune diseases caused by pathogenic antibodies via the inhibition of its interaction with IgG. We herein present the discovery of a small molecule that binds into a conserved cavity of the heterodimeric, extracellular domain composed of an alpha-chain and beta2-microglobulin (beta2m) (FcRnECD, 373 residues). X-ray crystallography was used alongside NMR at 100 kHz MAS with sedimented soluble protein to explore possibilities for refining the compound as an allosteric modulator. Proton-detected MAS NMR experiments on fully protonated [13C,15N]-labeled FcRnECD yielded ligand-induced chemical-shift perturbations (CSPs) for residues in the binding pocket and allosteric changes close to the interface of the two receptor heterodimers present in the asymmetric unit as well as potentially in the albumin interaction site. X-ray structures with and without ligand suggest the need for an optimized ligand to displace the alpha-chain with respect to beta2m, both of which participate in the FcRnECD-IgG interaction site. Our investigation establishes a method to characterize structurally small molecule binding to nondeuterated large proteins by NMR, even in their glycosylated form, which may prove highly valuable for structure-based drug discovery campaigns.

Insight into small molecule binding to the neonatal Fc receptor by X-ray crystallography and 100 kHz magic-angle-spinning NMR.,Stoppler D, Macpherson A, Smith-Penzel S, Basse N, Lecomte F, Deboves H, Taylor RD, Norman T, Porter J, Waters LC, Westwood M, Cossins B, Cain K, White J, Griffin R, Prosser C, Kelm S, Sullivan AH, Fox D 3rd, Carr MD, Henry A, Taylor R, Meier BH, Oschkinat H, Lawson AD PLoS Biol. 2018 May 21;16(5):e2006192. doi: 10.1371/journal.pbio.2006192. PMID:29782488<ref>PMID:29782488</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6c98" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fox III D]]
[[Category: Lukacs CM]]