Crystal structure of vespid phospholipase A1 reveals insights into the mechanism for cause of membrane dysfunction. (January 2016)

• Record Type: Journal Article
• Authors: Hou, Ming-Hon; Chuang, Chien-Ying; Ko, Tzu-Ping; Hu, Nien-Jen; Chou, Chia-Cheng; Shih, Yan-Ping; Ho, Chewn-Lang; Wang, Andrew H.-J.
• Is Part Of: Insect biochemistry and molecular biology. Volume 68(2016:Jan.)
• Page Start: 79
• Page End: 88
• Publication Date: 2016-01
• Subjects: Phospholipase A1 -- Lipase -- Hornet venom -- Phospholipid hydrolysis -- Membrane dysfunction -- X-ray crystallography; Insect biochemistry -- Periodicals; Insects -- Physiology -- Periodicals; Insects -- Molecular aspects -- Periodicals; Biochemistry -- Periodicals; Insectes -- Biochimie -- Périodiques; Insectes -- Composition -- Périodiques; Insectes -- Physiologie -- Périodiques; Insectes -- Aspect moléculaire -- Périodiques; Biochimie -- Périodiques; Biochemistry; Insect biochemistry; Insects -- Molecular aspects; Insects -- Physiology; Periodicals; 572.8157
• DOI: 10.1016/j.ibmb.2015.11.002
• Languages: English
• ISSNs: 0965-1748

Abstract

Abstract: Vespid phospholipase A1 (vPLA1 ) from the black-bellied hornet ( Vespa basalis ) catalyzes the hydrolysis of emulsified phospholipids and shows potent hemolytic activity that is responsible for its lethal effect. To investigate the mechanism of vPLA1 towards its function such as hemolysis and emulsification, we isolated vPLA1 from V. basalis venom and determined its crystal structure at 2.5 Å resolution. vPLA1 belongs to the α/β hydrolase fold family. It contains a tightly packed β-sheet surrounded by ten α-helices and a Gly-X-Ser-X-Gly motif, characteristic of a serine hydrolyase active site. A bound phospholipid was modeled into the active site adjacent to the catalytic Ser-His-Asp triad indicating that Gln95 is located at hydrogen-bonding distance from the substrate's phosphate group. Moreover, a hydrophobic surface comprised by the side chains of Phe53, Phe62, Met91, Tyr99, Leu197, Ala167 and Pro169 may serve as the acyl chain-binding site. vPLA1 shows global similarity to the N-terminal domain of human pancreatic lipase (HPL), but with some local differences. The lid domain and the β9 loop responsible for substrate selectivity in vPLA1 are shorter than in HPL. Thus, solvent-exposed hydrophilic residues can easily accommodate the polar head groups of phospholipids, thereby accounting for the high activity level of vPLA1 . Our result provides a potential explanation for the ability of vPLA1 to hydrolyze phospholipids of cell membrane. Graphical abstract: A schematic diagram of the mechanism for cause of membrane dysfunction by vPLA1 . Highlights: The first crystal structure of vPLA1 isolated from the black-bellied hornet. A mechanism for the hydrolysis of phospholipids by vPLA1 . The lid domain and β9 loop responsible for substrate selectivity were shorter in vPLA1. The functional deficiency of the lid domain was compensated by the longer α5 helix. Solvent-exposed hydrophilic residues accommodate the polar head groups of phospholipids.