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1tjj

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Revision as of 08:54, 21 March 2018

Human GM2 Activator Protein PAF complex

Structural highlights

1tjj is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , ,
Related:	1g13, 1pub, 1pu5
Gene:	GM2A (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SAP3_HUMAN] Defects in GM2A are the cause of GM2-gangliosidosis type AB (GM2GAB) [MIM:272750]; also known as Tay-Sachs disease AB variant. GM2-gangliosidosis is an autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. GM2GAB is characterized by GM2 gangliosides accumulation in the presence of both hexosaminidase A and B.^[1] ^[2] ^[3]

Function

[SAP3_HUMAN] The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity (By similarity). Binds gangliosides and stimulates ganglioside GM2 degradation. It stimulates only the breakdown of ganglioside GM2 and glycolipid GA2 by beta-hexosaminidase A. It extracts single GM2 molecules from membranes and presents them in soluble form to beta-hexosaminidase A for cleavage of N-acetyl-D-galactosamine and conversion to GM3.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

GM2-activator protein (GM2-AP) is a lipid transfer protein that has the ability to stimulate the enzymatic processing of gangliosides as well as T-cell activation through lipid presentation. Our previous X-ray crystallographic studies of GM2-AP have revealed a large lipid binding pocket as the central overall feature of the structure with non-protein electron density within this pocket suggesting bound lipid. To extend these studies, we present here the 2A crystal structure of GM2-AP complexed with platelet activating factor (PAF). PAF is a potent phosphoacylglycerol whose toxic patho-physiological effects can be inhibited by GM2-AP. The structure shows an ordered arrangement of two bound lipids and a fatty acid molecule. One PAF molecule binds in an extended conformation within the hydrophobic channel that has an open and closed conformation, and was seen to contain bound phospholipid in the low pH apo structure. The second molecule is submerged inside the pocket in a U-shaped conformation with its head group near the single polar residue S141. It was refined as lyso-PAF as it lacks electron density for the sn-2 acetate group. The alkyl chains of PAF interact through van der Waals' contacts, while the head groups bind in different environments with their phosphocholine moieties in contact with aromatic rings (Y137, F80). The structure has revealed further insights into the lipid binding properties of GM2-AP, suggesting an unexpected unique mode of lipid packaging that may explain the efficiency of GM2-AP in inhibiting the detrimental biological effects of PAF.

Evidence for lipid packaging in the crystal structure of the GM2-activator complex with platelet activating factor.,Wright CS, Mi LZ, Rastinejad F J Mol Biol. 2004 Sep 10;342(2):585-92. PMID:15327957^[4]

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

References

↑ Schroder M, Schnabel D, Suzuki K, Sandhoff K. A mutation in the gene of a glycolipid-binding protein (GM2 activator) that causes GM2-gangliosidosis variant AB. FEBS Lett. 1991 Sep 23;290(1-2):1-3. PMID:1915858
↑ Schroder M, Schnabel D, Hurwitz R, Young E, Suzuki K, Sandhoff K. Molecular genetics of GM2-gangliosidosis AB variant: a novel mutation and expression in BHK cells. Hum Genet. 1993 Nov;92(5):437-40. PMID:8244332
↑ Schepers U, Glombitza G, Lemm T, Hoffmann A, Chabas A, Ozand P, Sandhoff K. Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant. Am J Hum Genet. 1996 Nov;59(5):1048-56. PMID:8900233
↑ Wright CS, Mi LZ, Rastinejad F. Evidence for lipid packaging in the crystal structure of the GM2-activator complex with platelet activating factor. J Mol Biol. 2004 Sep 10;342(2):585-92. PMID:15327957 doi:10.1016/j.jmb.2004.07.063

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1tjj"

@@ Line 1: / Line 1: @@
 ==Human GM2 Activator Protein PAF complex==
 <StructureSection load='1tjj' size='340' side='right' caption='[[1tjj]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1g13|1g13]], [[1pub|1pub]], [[1pu5|1pu5]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GM2A ([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=1tjj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tjj OCA], [http://pdbe.org/1tjj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tjj RCSB], [http://www.ebi.ac.uk/pdbsum/1tjj PDBsum]</span></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=1tjj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tjj OCA], [http://pdbe.org/1tjj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tjj RCSB], [http://www.ebi.ac.uk/pdbsum/1tjj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1tjj ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tj/1tjj_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tj/1tjj_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1tjj

From Proteopedia

Revision as of 08:54, 21 March 2018

Human GM2 Activator Protein PAF complex

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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