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PDBsum entry 2agc
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protein ligands links
Lipid binding protein PDB id
2agc

 

 

 

 

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Contents
Protein chain
162 a.a. *
Ligands
MYR
DAO ×2
Waters ×66
* Residue conservation analysis
PDB id:
2agc
Name: Lipid binding protein
Title: Crystal structure of mouse gm2- activator protein
Structure: Ganglioside gm2 activator. Chain: a. Synonym: gm2-ap. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Organ: brain, kidney, liver. Gene: gm2a. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.50Å     R-factor:   0.233     R-free:   0.299
Authors: C.S.Wright,L.Z.Mi,S.Lee,F.Rastinejad
Key ref:
C.S.Wright et al. (2005). Crystal structure analysis of phosphatidylcholine-GM2-activator product complexes: evidence for hydrolase activity. Biochemistry, 44, 13510-13521. PubMed id: 16216074 DOI: 10.1021/bi050668w
Date:
26-Jul-05     Release date:   25-Oct-05    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q60648  (SAP3_MOUSE) -  Ganglioside GM2 activator from Mus musculus
Seq:
Struc: 		193 a.a.
162 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1021/bi050668w Biochemistry 44:13510-13521 (2005)
PubMed id: 16216074  
 
 
Crystal structure analysis of phosphatidylcholine-GM2-activator product complexes: evidence for hydrolase activity.
C.S.Wright, L.Z.Mi, S.Lee, F.Rastinejad.
 
  ABSTRACT  
 
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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21360616 J.Loch, A.Polit, A.Górecki, P.Bonarek, K.Kurpiewska, M.Dziedzicka-Wasylewska, and K.Lewiński (2011).
Two modes of fatty acid binding to bovine β-lactoglobulin-crystallographic and spectroscopic studies.
  J Mol Recognit, 24, 341-349.
PDB codes: 3npo 3nq3 3nq9
20388233 J.Horácková, N.Rudenko, M.Golovchenko, and L.Grubhoffer (2010).
Der-p2 ( Dermatophagoides pteronyssinus) allergen-like protein from the hard tick Ixodes ricinus - a novel member of ML (MD-2-related lipid-recognition) domain protein family.
  Parasitology, 137, 1139-1149.  
19486886 B.Rigat, H.Yeger, D.Shehnaz, and D.Mahuran (2009).
GM2 activator protein inhibits platelet activating factor signaling in rats.
  Biochem Biophys Res Commun, 385, 576-580.  
18952610 E.Starostina, A.Xu, H.Lin, and C.W.Pikielny (2009).
A Drosophila Protein Family Implicated in Pheromone Perception Is Related to Tay-Sachs GM2-Activator Protein.
  J Biol Chem, 284, 585-594.  
19720032 J.D.Mathias, Y.Ran, J.D.Carter, and G.E.Fanucci (2009).
Interactions of the GM2 activator protein with phosphatidylcholine bilayers: a site-directed spin-labeling power saturation study.
  Biophys J, 97, 1436-1444.  
19580763 Y.Ran, and G.E.Fanucci (2009).
Ligand extraction properties of the GM2 activator protein and its interactions with lipid vesicles.
  Biophys J, 97, 257-266.  
18519568 A.Teghanemt, R.L.Widstrom, T.L.Gioannini, and J.P.Weiss (2008).
Isolation of monomeric and dimeric secreted MD-2. Endotoxin.sCD14 and Toll-like receptor 4 ectodomain selectively react with the monomeric form of secreted MD-2.
  J Biol Chem, 283, 21881-21889.  
18462685 M.Rossmann, R.Schultz-Heienbrok, J.Behlke, N.Remmel, C.Alings, K.Sandhoff, W.Saenger, and T.Maier (2008).
Crystal structures of human saposins C andD: implications for lipid recognition and membrane interactions.
  Structure, 16, 809-817.
PDB codes: 2qyp 2r0r 2r1q 2rb3 2z9a
18694718 Y.Ran, and G.E.Fanucci (2008).
A dansyl fluorescence-based assay for monitoring kinetics of lipid extraction and transfer.
  Anal Biochem, 382, 132-134.  
17917069 T.L.Gioannini, and J.P.Weiss (2007).
Regulation of interactions of Gram-negative bacterial endotoxins with mammalian cells.
  Immunol Res, 39, 249-260.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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