Snake Venom Disintegrins: An Overview of their Interaction with Integrins

César, Pedro Henrique Souza; Braga, Mariana Aparecida; Trento, Marcus Vinícius Cardoso; Menaldo, Danilo L.; Marcussi, Silvana

doi:10.2174/1389450119666181022154737

Cited by 21 publications

(15 citation statements)

References 133 publications

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“…Most of their toxic effects are due to their interaction with cell surface ligands: inhibition of platelet aggregation, apoptosis, cytotoxicity. Moreover, they interfere with the functions of integrins by altering different cellular processes such as migration, adhesion or proliferation [94].…”

Section: Non-enzymatic Proteins 321 Disintegrinsmentioning

confidence: 99%

Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders

Larréché

Chippaux

Chevillard

et al. 2021

IJMS

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Toxins from Bothrops venoms targeting hemostasis are responsible for a broad range of clinical and biological syndromes including local and systemic bleeding, incoagulability, thrombotic microangiopathy and macrothrombosis. Beyond hemostais disorders, toxins are also involved in the pathogenesis of edema and in most complications such as hypovolemia, cardiovascular collapse, acute kidney injury, myonecrosis, compartmental syndrome and superinfection. These toxins can be classified as enzymatic proteins (snake venom metalloproteinases, snake venom serine proteases, phospholipases A2 and L-amino acid oxidases) and non-enzymatic proteins (desintegrins and C-type lectin proteins). Bleeding is due to a multifocal toxicity targeting vessels, platelets and coagulation factors. Vessel damage due to the degradation of basement membrane and the subsequent disruption of endothelial cell integrity under hydrostatic pressure and tangential shear stress is primarily responsible for bleeding. Hemorrhage is promoted by thrombocytopenia, platelet hypoaggregation, consumption coagulopathy and fibrin(ogen)olysis. Onset of thrombotic microangiopathy is probably due to the switch of endothelium to a prothrombotic phenotype with overexpression of tissue factor and other pro-aggregating biomarkers in association with activation of platelets and coagulation. Thrombosis involving large-caliber vessels in B. lanceolatus envenomation remains a unique entity, which exact pathophysiology remains poorly understood.

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Section: Non-enzymatic Proteins 321 Disintegrinsmentioning

confidence: 99%

Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders

Larréché

Chippaux

Chevillard

et al. 2021

IJMS

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“…As mentioned previously, there are several reports showing that some members of the P-II SVMP class do not contain the canonical RGD motif ( Calvete et al, 2005 ; Cesar et al, 2019 ; Rivas-Mercado and Garza-Ocañas, 2017 ). While some motifs share similarities, others are too varied and since the RGD motif is responsible for inhibition of platelet aggregation, members lacking this motif may have different activities and functions.…”

Section: Snake Venom Metalloproteinases (Svmps)mentioning

confidence: 83%

“…The RGD-motif is not totally conserved in all P-II members. There are copious reports of RGD variants such as KGD (lysine-glycine-aspartate), VGD (valine-glycine-aspartate), WGD (tryptophan-glycine-aspartate), MLD (methionine-leucine-aspartate), RTS (arginine-threonine-serine), KTS (lysine-threonine-serine) and so on ( Calvete et al, 2005 ; Cesar et al, 2019 ; Rivas-Mercado and Garza-Ocañas, 2017 ). The RGD-motif is embedded in a flexible loop constituted by the oligopeptide chain of 13 aminoacyl residues, which interact significantly with the integrin α IIB β 3 /GpIIb/IIIa inhibiting platelet aggregation ( Chung et al, 1999 ; Masuda et al, 2000 ).…”

Section: Snake Venom Metalloproteinases (Svmps)mentioning

confidence: 99%

Snake Venom Metalloproteinases (SVMPs): A structure-function update

et al. 2020

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Snake venom metalloproteinases (SVMPs) represent a diverse group of multi-domain proteins with several biological activities such as the ability to induce hemorrhage, proteolytic degradation of fibrinogen and fibrin, induction of apoptosis and inhibition of platelet aggregation. Due to these activities, SVMPs are responsible for many of the well-known pathological phenotypes in snake envenomations caused particularly by species from the Viperidae family and the Crotalinae subfamily. These proteins have been classified based on their size and domain structure into P–I, P-II and P-III classes. Comparatively, members of the P–I SVMPs possess the simplest structures, formed by the catalytic metalloproteinase domain only; the P-II SVMPs are moderately more complex, having the canonical disintegrin domain in addition to the metalloproteinase domain; members of the P-III class are more structurally varied, comprising the metalloproteinase, disintegrin-like, and cysteine-rich domains. Proteolytic cleavage, repeated domain loss and presence of other ancillary domains are responsible for structural diversities in the P-III class. However, studies continue to unveil the relationship between the structure and function of these proteins. In this review, we recovered evidences from literature on the structural peculiarities and functional classification of Snake Venom Metalloproteinases. In addition, we reflect on diversities that exist among each class while taking into account specific and up-to-date class-based activities.

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“…Many sequences or motifs have a crucial role in integrin binding. These motifs include, but are not limited to, RGD, RDD, KGD, RSD, WGD, and RYD identified in fibrinogen, thrombospondin, venom disintegrins, and others (Cesar et al, 2019;Springer et al, 2008;Subramanian et al, 2007). Analysis of the sequence of Drosophila Vago suggests the presence of a KGD motif, which was identified as an integrin binding motif (Matsuura et al, 2010;Ruoslahti, 1996).…”

Section: Discussionmentioning

confidence: 99%

Interferon functional analog activates antiviral Jak/Stat signaling through integrin in an arthropod

et al. 2021

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Drosophila Vago is a small antiviral peptide. Its ortholog in Culex mosquito was found to be an interferon-like cytokine that limits virus replication through activating Jak/Stat signaling. However, this activation is independent of Domeless, the sole homolog of vertebrate type I cytokine receptor. How Vago activates the Jak/Stat pathway remains unknown. Herein, we report this process is dependent on integrin in kuruma shrimp (Marsupenaeus japonicus). Shrimp Vago-like (MjVago-L) plays an antiviral role by activating the Jak/Stat pathway and inducing Stat-regulated Ficolin. Blocking integrin abrogates the role of MjVago-L. The interaction between MjVago-L and integrin b3 is confirmed. An Asp residue in MjVago-L is found critical for the interaction and MjVago-L's antiviral role. Moreover, Fak, a key adaptor of integrin signaling, mediates MjVago-L-induced Jak/Stat activation. Therefore, this study reveals that integrin, as the receptor of MjVago-L, mediates Jak/Stat activation. The establishment of the MjVago-L/integrin/Fak/Jak/Stat/Ficolin axis provides insights into antiviral cytokine signaling in invertebrates.

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Snake Venom Disintegrins: An Overview of their Interaction with Integrins

Cited by 21 publications

References 133 publications

Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders

Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders

Snake Venom Metalloproteinases (SVMPs): A structure-function update

Interferon functional analog activates antiviral Jak/Stat signaling through integrin in an arthropod

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