SNARE motif and neurotoxins

Rossetto, Ornella; Schiavo, Giampietro; Montecucco, Cesare; Poulain, Bernard; Deloye, F.; Lozzi, Luisa; Shone, Clifford C.

doi:10.1038/372415a0

Cited by 199 publications

(169 citation statements)

References 10 publications

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“…dictions of an a-helical structure for this region [17] and also suggests that any binding to the toxin within this region does not evoke the formation of such secondary structure.…”

Section: Discussionmentioning

confidence: 93%

“…Another possible mechanism is that, in addition to the site of cleavage, there are one or more sub-sites or recognition sites where the substrate binds to the neurotoxin. Recently, it has been suggested that a nine residue motif (residues 62 70; see Table 1), of which there are multiple copies in VAMP, syntaxin and SNAP-25 acts as a common recognition site for the clostridial toxins [17]. Strong evidence in favour of such a mechanism is the observation that the endopeptidase activity of one neurotoxin serotype can be inhibited by the presence another toxin serotype which suggests a common recognition element [17].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been suggested that a nine residue motif (residues 62 70; see Table 1), of which there are multiple copies in VAMP, syntaxin and SNAP-25 acts as a common recognition site for the clostridial toxins [17]. Strong evidence in favour of such a mechanism is the observation that the endopeptidase activity of one neurotoxin serotype can be inhibited by the presence another toxin serotype which suggests a common recognition element [17]. Data presented in the present study support the hypothesis of a sub-site for substrate binding in the case of BoNT/B.…”

Section: Discussionmentioning

confidence: 99%

“…Substitution or removal of both the Asp64 and Asp65 virtually abolished cleavage of the peptide by BoNT/B. Since Asp64,65 lie in a peptide sequence predicted to adopt an a-helical structure [17], the effect of disrupting such secondary structure was investigated by inserting a proline residues in this region. Substitution of Ala67 with a proline residue did not significantly reduce the cleavage rate by BoNT/B (Table la).…”

Section: Effect Of Substitution Of Charged Substrate Residues On Thementioning

confidence: 99%

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Substrate residues N‐terminal to the cleavage site of botulinum type B neurotoxin play a role in determining the specificity of its endopeptidase activity

Wictome¹,

Rossetto

Montecucco

et al. 1996

FEBS Letters

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Clostridium botulinum type B neurotoxin is a highly specific zinc-endopeptidase which cleaves vesicle-associated membrane protein (VAMP/synaptobrevin), a critical component of the vesicle docking/fusion mechanism. In this study, substrate residues flanking the N-terminal side of the cleavage site are shown to play a key role in enzyme substrate recognition. Two aspartate residues in this region are identified as critical determinants of the neurotoxin's specificity. These findings are discussed in relation to the mechanism by which botulinum type B neurotoxin cleaves its substrate.

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“…dictions of an a-helical structure for this region [17] and also suggests that any binding to the toxin within this region does not evoke the formation of such secondary structure.…”

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Effect Of Substitution Of Charged Substrate Residues On Thementioning

confidence: 99%

See 2 more Smart Citations

Substrate residues N‐terminal to the cleavage site of botulinum type B neurotoxin play a role in determining the specificity of its endopeptidase activity

Wictome¹,

Rossetto

Montecucco

et al. 1996

FEBS Letters

Self Cite

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“…As stated above, insulin secretory vesicles must fuse with the plasma membrane in order to discharge their contents. Docking of vesicles is facilitated by a set of SNARE proteins (soluble N-ethylmaleimide sensitive factor attachment protein SNAP receptors) originally described in synaptic vesicle-membrane fusion (Rossetto et al, 1994). SNARE proteins form a superfamily of proteins that consists of 36 members in humans (Jahn and Scheller, 2006).…”

Section: Exocytosis Of Insulin Secretory Vesiclesmentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

583

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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Common and distinct fusion proteins in axonal growth and transmitter release

Osen-Sand¹,

Staple²,

Naldi³

et al. 1996

J. Comp. Neurol.

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196

124

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In many areas of science multiple sets of data are collected pertaining to the same system. Examples are food products which are characterized by different sets of variables, bio-processes which are on-line sampled with different instruments, or biological systems of which different genomics measurements are obtained. Data fusion is concerned with analyzing such sets of data simultaneously to arrive at a global view of the system under study. One of the upcoming areas of data fusion is exploring whether the data sets have something in common or not. This gives insight into common and distinct variation in each data set, thereby facilitating understanding the relationships between the data sets. Unfortunately, research on methods to distinguish common and distinct components is fragmented, both in terminology as well as in methods: there is no common ground which hampers comparing methods and understanding their relative merits. This paper provides a unifying framework for this subfield of data fusion by using rigorous arguments from linear algebra. The most frequently used methods for distinguishing common and distinct components are explained in this framework and some practical examples are given of these methods in the areas of (medical) biology and food science.

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SNARE motif and neurotoxins

Cited by 199 publications

References 10 publications

Substrate residues N‐terminal to the cleavage site of botulinum type B neurotoxin play a role in determining the specificity of its endopeptidase activity

Substrate residues N‐terminal to the cleavage site of botulinum type B neurotoxin play a role in determining the specificity of its endopeptidase activity

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Common and distinct fusion proteins in axonal growth and transmitter release

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