View source for 4ywt


==Crystal structure of full-length glypican-1 core protein after controlled crystal dehydration to 87% relative humidity==
<StructureSection load='4ywt' size='340' side='right'caption='[[4ywt]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ywt]] 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=4YWT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YWT 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]] 2.38&#8491;</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4ywt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ywt OCA], [https://pdbe.org/4ywt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ywt RCSB], [https://www.ebi.ac.uk/pdbsum/4ywt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ywt ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GPC1_HUMAN GPC1_HUMAN] Biliary atresia. Associates (via the heparan sulfate side chains) with fibrillar APP-beta amyloid peptides in primitive and classic amyloid plaques and may be involved in the deposition of these senile plaques in the Alzheimer disease (AD) brain.  Misprocessing of GPC1 is found in fibroblasts of patients with Niemann-Pick Type C1 disease. This is due to the defective deaminative degradation of heparan sulfate chains.
== Function ==
[https://www.uniprot.org/uniprot/GPC1_HUMAN GPC1_HUMAN] Cell surface proteoglycan that bears heparan sulfate. Binds, via the heparan sulfate side chains, alpha-4 (V) collagen and participates in Schwann cell myelination (By similarity). May act as a catalyst in increasing the rate of conversion of prion protein PRPN(C) to PRNP(Sc) via associating (via the heparan sulfate side chains) with both forms of PRPN, targeting them to lipid rafts and facilitating their interaction. Required for proper skeletal muscle differentiation by sequestering FGF2 in lipid rafts preventing its binding to receptors (FGFRs) and inhibiting the FGF-mediated signaling.<ref>PMID:19936054</ref> <ref>PMID:21642435</ref> 
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== Publication Abstract from PubMed ==
Glypicans are multifunctional cell surface proteoglycans involved in several important cellular signalling pathways. Glypican-1 (Gpc1) is the predominant heparan sulphate (HS) proteoglycan in the developing and adult human brain. The two N-linked glycans and the C-terminal domain that attaches the core protein to the cell membrane are not resolved in the Gpc1 crystal structure. Therefore we have studied Gpc1 using crystallography, small-angle X-ray scattering and chromatographic approaches to elucidate the composition, structure and function of the N-glycans and the C-terminus, and also the topology of Gpc1 with respect to the membrane. The C-terminus is shown to be highly flexible in solution, but it orients the core protein transverse to the membrane, directing a surface evolutionarily conserved in Gpc1 orthologues towards the membrane, where it may interact with signalling molecules and/or membrane receptors on the cell surface, or even the enzymes involved in HS substitution in the Golgi apparatus Furthermore, the N-glycans are shown to extend the protein stability and lifetime by protection against proteolysis and aggregation.

Structural aspects of N-glycosylations and the C-terminal region in human glypican-1.,Awad W, Adamczyk B, Ornros J, Karlsson NG, Mani K, Logan DT J Biol Chem. 2015 Jul 22. pii: jbc.M115.660878. PMID:26203194<ref>PMID:26203194</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Awad W]]
[[Category: Logan DT]]
[[Category: Mani K]]