This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2af9

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 07:14, 9 May 2018

Crystal Structure analysis of GM2-Activator protein complexed with phosphatidylcholine

Structural highlights

2af9 is a 1 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:	1tjj, 1pub, 1pu5, 1g13
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 (GM2AP) is a lysosomal lipid transfer protein with important biological roles in ganglioside catabolism, phospholipid metabolism, and T-cell activation. Previous studies of crystal structures of GM2AP complexed with the physiological ligand GM2 and platelet activating factor (PAF) have shown binding at two specific locations within the spacious apolar pocket and an ordering effect of endogenous resident lipids. To investigate the structural basis of phospholipid binding further, GM2AP was cocrystallized with phosphatidylcholine (PC), known to interact with GM2AP. Analysis of three crystal forms revealed binding of single chain lipids and fatty acids only and surprisingly not intact PC. The regions of best defined electron density are consistent with the presence of lyso-PC and oleic acid, which constitute deacylation products of PC. Their acyl tails are in stacking contact with shorter, less well-defined stretches of electron density that may represent resident fatty acids. The GM2AP associated hydrolytic activity that generates lyso-PC was further confirmed by mass spectrometry and enzymatic assays. In addition, we report the structures of (i) mutant Y137S, assessing the role of Tyr137 in lipid transfer via the hydrophobic cleft, and (ii) apo-mouse GM2AP, revealing a hydrophobic pocket with a constricted opening. Our structural results provide new insights into the biological functions of GM2AP. The combined effect of hydrolytic and lipid transfer properties has profound implications in cellular signaling.

Crystal structure analysis of phosphatidylcholine-GM2-activator product complexes: evidence for hydrolase activity.,Wright CS, Mi LZ, Lee S, Rastinejad F Biochemistry. 2005 Oct 18;44(41):13510-21. PMID:16216074^[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, Lee S, Rastinejad F. Crystal structure analysis of phosphatidylcholine-GM2-activator product complexes: evidence for hydrolase activity. Biochemistry. 2005 Oct 18;44(41):13510-21. PMID:16216074 doi:http://dx.doi.org/10.1021/bi050668w

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/2af9"

@@ Line 1: / Line 1: @@
 ==Crystal Structure analysis of GM2-Activator protein complexed with phosphatidylcholine==
 <StructureSection load='2af9' size='340' side='right' caption='[[2af9]], [[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">[[1tjj|1tjj]], [[1pub|1pub]], [[1pu5|1pu5]], [[1g13|1g13]]</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=2af9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2af9 OCA], [http://pdbe.org/2af9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2af9 RCSB], [http://www.ebi.ac.uk/pdbsum/2af9 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=2af9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2af9 OCA], [http://pdbe.org/2af9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2af9 RCSB], [http://www.ebi.ac.uk/pdbsum/2af9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2af9 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/af/2af9_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/af/2af9_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2af9 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">

2af9

From Proteopedia

Revision as of 07:14, 9 May 2018

Crystal Structure analysis of GM2-Activator protein complexed with phosphatidylcholine

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox