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5eli

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Revision as of 09:13, 1 November 2017

Triggering receptor expressed on myeloid cells 2

Structural highlights

5eli is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	TREM2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TREM2_HUMAN] Progressive non-fluent aphasia;Amyotrophic lateral sclerosis;Nasu-Hakola disease;Semantic dementia;Behavioral variant of frontotemporal dementia. The disease is caused by mutations affecting the gene represented in this entry.

Function

[TREM2_HUMAN] May have a role in chronic inflammations and may stimulate production of constitutive rather than inflammatory chemokines and cytokines. Forms a receptor signaling complex with TYROBP and triggers activation of the immune responses in macrophages and dendritic cells.^[1]

Publication Abstract from PubMed

Genetic variations in the myeloid immune receptor TREM2 are linked to several neurodegenerative diseases. To determine how TREM2 variants contribute to these diseases, we performed structural and functional studies of wild-type and variant proteins. Our 3.1 A TREM2 crystal structure revealed that mutations found in Nasu-Hakola disease are buried whereas Alzheimer's disease risk variants are found on the surface, suggesting that these mutations have distinct effects on TREM2 function. Biophysical and cellular methods indicate that Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer's risk variants impact binding to a TREM2 ligand. Additionally, the Alzheimer's risk variants appear to epitope map a functional surface on TREM2 that is unique within the larger TREM family. These findings provide a guide to structural and functional differences among genetic variants of TREM2, indicating that therapies targeting the TREM2 pathway should be tailored to these genetic and functional differences with patient-specific medicine approaches for neurodegenerative disorders.

Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms.,Kober DL, Alexander-Brett JM, Karch CM, Cruchaga C, Colonna M, Holtzman MJ, Brett TJ Elife. 2016 Dec 20;5. pii: e20391. doi: 10.7554/eLife.20391. PMID:27995897^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bouchon A, Dietrich J, Colonna M. Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol. 2000 May 15;164(10):4991-5. PMID:10799849
↑ Kober DL, Alexander-Brett JM, Karch CM, Cruchaga C, Colonna M, Holtzman MJ, Brett TJ. Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms. Elife. 2016 Dec 20;5. pii: e20391. doi: 10.7554/eLife.20391. PMID:27995897 doi:http://dx.doi.org/10.7554/eLife.20391

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5eli"

@@ Line 3: / Line 3: @@
 <StructureSection load='5eli' size='340' side='right' caption='[[5eli]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5eli]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ELI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ELI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5eli]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ELI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ELI FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TREM2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5eli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eli OCA], [http://pdbe.org/5eli PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eli RCSB], [http://www.ebi.ac.uk/pdbsum/5eli PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eli ProSAT]</span></td></tr>
 </table>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Brett, T J]]
 [[Category: Kober, D L]]

5eli

From Proteopedia

Revision as of 09:13, 1 November 2017

Triggering receptor expressed on myeloid cells 2

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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