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Crystal Structure o...
Crystal Structure of the Botulinum Neurotoxin Type G Binding Domain : Insight into Cell Surface Binding
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- Stenmark, Pål (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Dong, Min (författare)
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Dupuy, Jerome (författare)
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Chapman, Edwin R. (författare)
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Stevens, Raymond C. (författare)
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(creator_code:org_t)
- Elsevier BV, 2010
- 2010
- Engelska.
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 397:5, s. 1287-1297
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-angstrom X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantly reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
Nyckelord
- botulinum
- neurotoxin
- synaptotagmin
- ganglioside
- toxin
- NATURAL SCIENCES
- NATURVETENSKAP
- biokemi
- Biochemistry
- Structural Biology
- strukturbiologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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