Research

Jump to: Review

971 KiB

Open AccessArticle

Molecular Conversion of Muscarinic Acetylcholine Receptor M₅ to Muscarinic Toxin 7 (MT7)-Binding Protein

by Sergio Rondinelli, Katja Näreoja and Johnny Näsman

Toxins 2011, 3(11), 1393-1404; https://doi.org/10.3390/toxins3111393 - 11 Nov 2011

Cited by 4 | Viewed by 6134

Muscarinic toxin 7 (MT7) is a mamba venom peptide that binds selectively to the M₁ muscarinic acetylcholine receptor. We have previously shown that the second (ECL2) and third (ECL3) extracellular loops of the M₁ receptor are critically involved in binding the [...] Read more.

Muscarinic toxin 7 (MT7) is a mamba venom peptide that binds selectively to the M₁ muscarinic acetylcholine receptor. We have previously shown that the second (ECL2) and third (ECL3) extracellular loops of the M₁ receptor are critically involved in binding the peptide. In this study we used a mutagenesis approach on the M₅ subtype of the receptor family to find out if this possesses a similar structural architecture in terms of toxin binding as the M₁ receptor. An M₅ receptor construct (M₅-E¹⁷⁵Y¹⁸⁴E⁴⁷⁴), mutated at the formerly deciphered critical residues on ECL2 and 3, gained the ability to bind MT7, but with rather low affinity as determined in a functional assay (apparent K_i = 24 nM; apparent K_i for M₁ = 0.5 nM). After screening for different domains and residues, we found a specific residue (P¹⁷⁹ to L in M₅) in the middle portion of ECL2 that was necessary for high affinity binding of MT7 (M₅-EL¹⁷⁹YE, apparent K_i = 0.5 nM). Mutation of P¹⁷⁹ to A confirmed a role for the leucine side chain in the binding of MT7. Together the results reveal new binding interactions between receptors and the MT7 peptide and strengthen the hypothesis that ECL2 sequence is of utmost importance for MT binding to muscarinic receptors. Full article

(This article belongs to the Special Issue Snake Venoms)

► Show Figures

Figure 1

687 KiB

Open AccessArticle

Molecular Analysis of the Interaction of the Snake Venom Rhodocytin with the Platelet Receptor CLEC-2

by Aleksandra A. Watson and Christopher A. O’Callaghan

Toxins 2011, 3(8), 991-1003; https://doi.org/10.3390/toxins3080991 - 10 Aug 2011

Cited by 9 | Viewed by 6536

Abstract

The Malayan pit viper, Calloselasma rhodostoma, produces a potent venom toxin, rhodocytin (aggretin) which causes platelet aggregation. Rhodocytin is a ligand for the receptor CLEC-2 on the surface of platelets. The interaction of these two molecules initiates a signaling pathway which results [...] Read more.

The Malayan pit viper, Calloselasma rhodostoma, produces a potent venom toxin, rhodocytin (aggretin) which causes platelet aggregation. Rhodocytin is a ligand for the receptor CLEC-2 on the surface of platelets. The interaction of these two molecules initiates a signaling pathway which results in platelet activation and aggregation. We have previously solved the crystal structures of CLEC-2 and of rhodocytin, and have proposed models by which tetrameric rhodocytin may interact with either two monomers of CLEC-2, or with one or two copies of dimeric CLEC-2. In the current study we use a range of approaches to analyze the molecular interfaces and dynamics involved in the models of the interaction of rhodocytin with either one or two copies of dimeric CLEC-2, and their implications for clustering of CLEC-2 on the platelet surface. Full article

(This article belongs to the Special Issue Snake Venoms)

► Show Figures

Graphical abstract

Review

Jump to: Research

665 KiB

Open AccessReview

Pharmacological Aspects of Vipera xantina palestinae Venom

by Tatjana Momic, Franziska T. Arlinghaus, Hadar Arien-Zakay, Jeoshua Katzhendler, Johannes A. Eble, Cezary Marcinkiewicz and Philip Lazarovici

Toxins 2011, 3(11), 1420-1432; https://doi.org/10.3390/toxins3111420 - 14 Nov 2011

Cited by 26 | Viewed by 7121

Abstract

In Israel, Vipera xantina palestinae (V.x.p.) is the most common venomous snake, accounting for several hundred cases of envenomation in humans and domestic animals every year, with a mortality rate of 0.5 to 2%. In this review we will briefly address [...] Read more.

In Israel, Vipera xantina palestinae (V.x.p.) is the most common venomous snake, accounting for several hundred cases of envenomation in humans and domestic animals every year, with a mortality rate of 0.5 to 2%. In this review we will briefly address the research developments relevant to our present understanding of the structure and function of V.x.p. venom with emphasis on venom disintegrins. Venom proteomics indicated the presence of four families of pharmacologically active compounds: (i) neurotoxins; (ii) hemorrhagins; (iii) angioneurin growth factors; and (iv) different types of integrin inhibitors. Viperistatin, a α1β1selective KTS disintegrin and VP12, a α2β1 selective C-type lectin were discovered. These snake venom proteins represent promising tools for research and development of novel collagen receptor selective drugs. These discoveries are also relevant for future improvement of antivenom therapy towards V.x.p. envenomation. Full article

(This article belongs to the Special Issue Snake Venoms)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Snake Venoms

Share This Special Issue

Special Issue Editor

Published Papers (3 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI