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==Crystal Structure of E2 domain of Human Amyloid Precursor-Like Protein 1== | |||
<StructureSection load='3pmr' size='340' side='right' caption='[[3pmr]], [[Resolution|resolution]] 2.11Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3pmr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PMR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PMR FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APLP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3pmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pmr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pmr RCSB], [http://www.ebi.ac.uk/pdbsum/3pmr PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Amyloid precursor protein (APP) is genetically linked to Alzheimer's disease. APP is a type I membrane protein, and its oligomeric structure is potentially important because this property may play a role in its function or affect the processing of the precursor by the secretases to generate amyloid beta-peptide. Several independent studies have shown that APP can form dimers in the cell, but how it dimerizes remains controversial. At least three regions of the precursor, including a centrally located and conserved domain called E2, have been proposed to contribute to dimerization. Here we report two new crystal structures of E2, one from APP and the other from APLP1, a mammalian APP homologue. Comparison with an earlier APP structure, which was determined in a different space group, shows that the E2 domains share a conserved and antiparallel mode of dimerization. Biophysical measurements in solution show that heparin binding induces E2 dimerization. The 2.1 A resolution electron density map also reveals phosphate ions that are bound to the protein surface. Mutational analysis shows that protein residues interacting with the phosphate ions are also involved in heparin binding. The locations of two of these residues, Arg-369 and His-433, at the dimeric interface suggest a mechanism for heparin-induced protein dimerization. | |||
The E2 Domains of APP and APLP1 Share a Conserved Mode of Dimerization.,Lee S, Xue Y, Hu J, Wang Y, Liu X, Demeler B, Ha Y Biochemistry. 2011 May 26. PMID:21574595<ref>PMID:21574595</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Demeler, B | [[Category: Demeler, B]] | ||
[[Category: Ha, Y | [[Category: Ha, Y]] | ||
[[Category: Hu, J | [[Category: Hu, J]] | ||
[[Category: Lee, S | [[Category: Lee, S]] | ||
[[Category: Liu, X | [[Category: Liu, X]] | ||
[[Category: Wang, Y | [[Category: Wang, Y]] | ||
[[Category: Xue, Y | [[Category: Xue, Y]] | ||
[[Category: Cell adhesion]] | [[Category: Cell adhesion]] | ||
[[Category: Heparin binding]] | [[Category: Heparin binding]] | ||
Revision as of 13:43, 19 December 2014
Crystal Structure of E2 domain of Human Amyloid Precursor-Like Protein 1Crystal Structure of E2 domain of Human Amyloid Precursor-Like Protein 1
Structural highlights
Publication Abstract from PubMedAmyloid precursor protein (APP) is genetically linked to Alzheimer's disease. APP is a type I membrane protein, and its oligomeric structure is potentially important because this property may play a role in its function or affect the processing of the precursor by the secretases to generate amyloid beta-peptide. Several independent studies have shown that APP can form dimers in the cell, but how it dimerizes remains controversial. At least three regions of the precursor, including a centrally located and conserved domain called E2, have been proposed to contribute to dimerization. Here we report two new crystal structures of E2, one from APP and the other from APLP1, a mammalian APP homologue. Comparison with an earlier APP structure, which was determined in a different space group, shows that the E2 domains share a conserved and antiparallel mode of dimerization. Biophysical measurements in solution show that heparin binding induces E2 dimerization. The 2.1 A resolution electron density map also reveals phosphate ions that are bound to the protein surface. Mutational analysis shows that protein residues interacting with the phosphate ions are also involved in heparin binding. The locations of two of these residues, Arg-369 and His-433, at the dimeric interface suggest a mechanism for heparin-induced protein dimerization. The E2 Domains of APP and APLP1 Share a Conserved Mode of Dimerization.,Lee S, Xue Y, Hu J, Wang Y, Liu X, Demeler B, Ha Y Biochemistry. 2011 May 26. PMID:21574595[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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