Rational attenuation of elapid long-chain neurotoxin by targeted residue substitution and disulfide architecture simplification: implications for receptor interaction and immune recognition

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  Rational attenuation of elapid long-chain neurotoxin by targeted residue substitution and disulfide architecture simplification: implications for receptor interaction and immune recognition Abstract Elapid long-chain neurotoxins (LNTxs) exert their toxicity through high-affinity binding to nicotinic acetylcholine receptors (nAChRs). Specific residues mediate this process, including basic (Lys23, Arg33, Arg36, Lys49), structural (Cys26, Cys30), and aromatic (Phe29) amino acids. To investigate the functional and immunogenic implications of modifying these residues, we designed two recombinant variants of a consensus LNTx. The first variant, rLcNTx V1, contains charge-reversal mutations at four key basic positions, while the second, rLcNTx V2, lacks the segment corresponding to the fifth disulfide bond. We expressed both variants in Escherichia coli Origami cells. rLcNTx V1 was recovered in a soluble form, but rLcNTx V2 was present only in inclusion bodies. We assessed the binding ...

Neglected no longer: Phylogenomic resolution of higher-level relationships in Solifugae

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Neglected no longer: Phylogenomic resolution of higher-level relationships in Solifugae

Summary
Advanced sequencing technologies have expedited resolving higher-level arthropod relationships. Yet, dark branches persist, principally among groups occurring in cryptic habitats. Among chelicerates, Solifugae (“camel spiders”) is the last order lacking a higher-level phylogeny and thus, historically characterized as “neglected [arachnid] cousins”. Though renowned for aggression, remarkable running speed, and xeric adaptation, inferring solifuge relationships has been hindered by inaccessibility of diagnostic morphological characters, whereas molecular investigations have been limited to one of 12 recognized families. Our phylogenomic dataset via capture of ultraconserved elements sampling all extant families recovered a well-resolved phylogeny, with two distinct groups of New World taxa nested within a broader Paleotropical radiation. Divergence times using fossil calibrations inferred Solifugae radiated by the Permian, and most families diverged pre-Paleogene-Cretaceous extinction, largely driven by continental breakup. We establish Boreosolifugae new suborder uniting five Laurasian families, and Australosolifugae new suborder uniting seven Gondwanan families using morphological and biogeographic signal.

Siddharth S. Kulkarni,Hugh G. Steiner,Erika L. Garcia,Hernán Iuri,R. Ryan Jones,Jesús A. Ballesteros,Guilherme Gainett,Matthew R. Graham,Danilo Harms,Robin Lyle,Andrés A. Ojanguren-Affilastro,Carlos E. Santibañez-López,Gustavo Silva de Miranda et al.

Publication: 

iScience (PDF)

Publisher: 

Elsevier

Date: 

Available online 19 August 2023