Comparative Biochemical, Structural, and Functional Analysis of Recombinant Phospholipases D from Three ILoxosceles/I Spider Venoms

Spiders of Loxosceles genus are widely distributed and their venoms contain phospholipases D (PLDs), which degrade phospholipids and trigger inflammatory responses, dermonecrosis, hematological changes, and renal injuries. Biochemical, functional, and structural properties of three recombinant PLDs...

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Bibliographic Details
Published in:	International journal of molecular sciences Vol. 24; no. 15
Main Authors:	da Justa, Hanna Câmara, Hernández González, Jorge Enrique, Vuitika, Larissa, Mariutti, Ricardo Barros, Magnago, Pedro Augusto Ma, de Moraes, Fábio Rogério, Senff-Ribeiro, Andrea, Gremski, Luiza Helena, Arni, Raghuvir Krishnaswamy, Veiga, Silvio Sanches
Format:	Journal Article
Language:	English
Published:	MDPI AG 01-07-2023
Subjects:	Amino acids Comparative analysis Lipids Molecular dynamics Phospholipases Venom Brazil
Online Access:	Get full text
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Summary:	Spiders of Loxosceles genus are widely distributed and their venoms contain phospholipases D (PLDs), which degrade phospholipids and trigger inflammatory responses, dermonecrosis, hematological changes, and renal injuries. Biochemical, functional, and structural properties of three recombinant PLDs from L. intermedia, L. laeta, and L. gaucho, the principal species clinically relevant in South America, were analyzed. Sera against L. gaucho and L. laeta PLDs strongly cross-reacted with other PLDs, but sera against L. intermedia PLD mostly reacted with homologous molecules, suggesting underlying structural and functional differences. PLDs presented a similar secondary structure profile but distinct melting temperatures. Different methods demonstrated that all PLDs cleave sphingomyelin and lysophosphatidylcholine, but L. gaucho and L. laeta PLDs excelled. L. gaucho PLD showed greater “in vitro” hemolytic activity. L. gaucho and L. laeta PLDs were more lethal in assays with mice and crickets. Molecular dynamics simulations correlated their biochemical activities with differences in sequences and conformations of specific surface loops, which play roles in protein stability and in modulating interactions with the membrane. Despite the high similarity, PLDs from L. gaucho and L. laeta venoms are more active than L. intermedia PLD, requiring special attention from physicians when these two species prevail in endemic regions.
ISSN:	1422-0067
DOI:	10.3390/ijms241512006