1TJJ

Human GM2 Activator Protein PAF complex

Summary for 1TJJ

• Entry DOI: 10.2210/pdb1tjj/pdb
• Related: 1G13 1PU5 1PUB
• Descriptor: Ganglioside GM2 activator, ACETATE ION, CHLORIDE ION, ... (9 entities in total)
• Functional Keywords: platelet activating factor, lipid binding pocket, beta-cup topology, protein dynamics, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P17900
• Total number of polymer chains: 3
• Total formula weight: 57964.83

Authors

Wright, C.S.,Mi, L.-Z.,Rastinejad, F. (deposition date: 2004-06-04, release date: 2004-12-07, Last modification date: 2024-11-20)

Primary citation

Wright, C.S.,Mi, L.-Z.,Rastinejad, F.
Evidence for lipid packaging in the crystal structure of the GM2-activator complex with platelet activating factor
J.Mol.Biol., 342:585-592, 2004

PubMed Abstract: 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.

PubMed: 15327957
DOI: 10.1016/j.jmb.2004.07.063

Experimental method

X-RAY DIFFRACTION (2 Å)