View source for 1pxu


==Crystal structure of chicken NtA from a eukaryotic source at 2.2A resolution==
<StructureSection load='1pxu' size='340' side='right'caption='[[1pxu]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1pxu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PXU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PXU 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]] 2.2&#8491;</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=1pxu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pxu OCA], [https://pdbe.org/1pxu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pxu RCSB], [https://www.ebi.ac.uk/pdbsum/1pxu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pxu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AGRIN_CHICK AGRIN_CHICK] Isoform 1: heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Component of the AGRN-LRP4 receptor complex that induces the phosphorylation and activation of MUSK. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Calcium ions are required for maximal AChR clustering. AGRN funtion in neurons is highly regulated by alternative splicing, glycan binding and proteolytic processing. Modulates calcium ion homestasis in neurons, specifically by inducing an increase in cytoplasmic calcium ions. Functions differentially in the central nervous system (CNS) by inhibiting the alpha(3)-subtype of Na+/K+-ATPase and evoking depolarization at CNS synapses.<ref>PMID:7860635</ref> <ref>PMID:11425874</ref> <ref>PMID:15198666</ref> <ref>PMID:17012237</ref> <ref>PMID:17649979</ref> <ref>PMID:19940118</ref> <ref>PMID:22984437</ref>   Isoform 9: transmembrane agrin (TM-agrin), the predominant form in neurons of the brain, induces dendritic filopodia and synapse formation in mature hippocampal neurons in large part due to the attached glycosaminoglycan chains and the action of Rho-family GTPases.<ref>PMID:7860635</ref> <ref>PMID:11425874</ref> <ref>PMID:15198666</ref> <ref>PMID:17012237</ref> <ref>PMID:17649979</ref> <ref>PMID:19940118</ref> <ref>PMID:22984437</ref>   Isoform 2, isoform 4 and isoform 7: muscle agrin isoforms, which lack the 8-amino acid insert at the 'B' site, but with the insert at the'A' site have no AChr clustering activity nor MUSK activation but bind heparin. Bind alpha-dystroglycan with lower affinity.<ref>PMID:7860635</ref> <ref>PMID:11425874</ref> <ref>PMID:15198666</ref> <ref>PMID:17012237</ref> <ref>PMID:17649979</ref> <ref>PMID:19940118</ref> <ref>PMID:22984437</ref>   Isoform 5: muscle agrin A0B0 lacking inserts at both 'A' and 'B' sites has no heparin-binding nor AChR clustering activity but binds strongly alpha-dystroglycan.<ref>PMID:7860635</ref> <ref>PMID:11425874</ref> <ref>PMID:15198666</ref> <ref>PMID:17012237</ref> <ref>PMID:17649979</ref> <ref>PMID:19940118</ref> <ref>PMID:22984437</ref>   Agrin N-terminal 110 kDa subunit: is involved in modulation of growth factor signaling (By similarity). Involved also in the regulation of neurite outgrowth probably due to the presence of the glycosaminoglcan (GAG) side chains of heparan and chondroitin sulfate attached to the Ser/Thr- and Gly/Ser-rich regions. Also involved in modulation of growth factor signaling.<ref>PMID:7860635</ref> <ref>PMID:11425874</ref> <ref>PMID:15198666</ref> <ref>PMID:17012237</ref> <ref>PMID:17649979</ref> <ref>PMID:19940118</ref> <ref>PMID:22984437</ref>   Agrin C-terminal 22 kDa fragment: this released fragment is important for agrin signaling and to exert a maximal dendritic filopodia-inducing effect. All 'B' splice variants of this fragment also show an increase in the number of filopodia.<ref>PMID:7860635</ref> <ref>PMID:11425874</ref> <ref>PMID:15198666</ref> <ref>PMID:17012237</ref> <ref>PMID:17649979</ref> <ref>PMID:19940118</ref> <ref>PMID:22984437</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Agrin is a key organizer for postsynaptic differentiation at the neuromuscular junction (NMJ). This activity requires the binding of agrin to the synaptic basal lamina via its N-terminal (NtA) domain. It has been suggested that this binding is mediated by conserved amino acids in the gamma 1 chain of laminin. Here, we report the crystal structure of chicken NtA expressed in eukaryotic HEK293 cells. In contrast to the previously published structure [Stetefeld, J., Jenny, M., Schulthess, T., Landwehr, R., Schumacher, B., Frank, S., Ruegg, M.A., Engel, J., Kammerer, R.A., 2001. The laminin-binding domain of agrin is structurally related to N-TIMP-1. Nat. Struct. Biol., 8, 705-709.], which was derived from the NtA domain expressed in E. coli, the new data show that the N-terminal tail region (amino acid residues Asn1-Arg5) is highly structured. Moreover, the disulfide bridge between Cys2 and Cys74 was also present. In addition, we show that the binding of NtA requires the gamma 1 chain of laminin and is not greatly affected by the composition of beta chains. These results confirm a model of the NtA-laminin complex where conserved amino acids in the gamma 1 chain are prerequisite for the binding to agrin and they further emphasize that the source of protein can be critical in structure determination.

Structure and laminin-binding specificity of the NtA domain expressed in eukaryotic cells.,Mascarenhas JB, Ruegg MA, Sasaki T, Eble JA, Engel J, Stetefeld J Matrix Biol. 2005 Jan;23(8):507-13. Epub 2004 Dec 30. PMID:15694127<ref>PMID:15694127</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1pxu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Agrin 3D structures|Agrin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Stetefeld J]]