{"product_id":"design-and-synthesis-of-modified-snare-proteins-with-respect-to-the-a-snap-nsf-mediated-disassembly-von-annika-groschner","title":"Design and Synthesis of Modified SNARE Proteins with Respect to the ¿¿SNAP\/NSF Mediated Disassembly","description":"\u003cp\u003eSoluble N-ethylmaleimide-sensitive attachment receptor (SNARE) proteins are the\u003c\/p\u003e\u003cp\u003ekey players in membrane fusion. Localized in opposed membranes, they assemble via\u003c\/p\u003e\u003cp\u003ethe SNARE motif in a stable four-helix bundle bringing the membranes close to each\u003c\/p\u003e\u003cp\u003eother and promoting membrane fusion by using the energy release during complex\u003c\/p\u003e\u003cp\u003eformation. SNARE complex assembly is regulated by several proteins. One of these,\u003c\/p\u003e\u003cp\u003eComplexin, is known to partially associate with the core complex, it may stabilize\u003c\/p\u003e\u003cp\u003eSNARE complex intermediates and unbinds upon calcium trigger. Nevertheless, the\u003c\/p\u003e\u003cp\u003eexact function of Complexin is still under discussion. After membrane fusion the\u003c\/p\u003e\u003cp\u003erecycling of free SNARE proteins is mediated by the AAA+ protein NSF in conjunction\u003c\/p\u003e\u003cp\u003ewith its cofactor a-SNAP. Afterwards, the individual SNARE proteins are available for\u003c\/p\u003e\u003cp\u003eanother round of membrane fusion.\u003c\/p\u003e\u003cp\u003eTo date, no effective model systems for preventing or at least decelerating the\u003c\/p\u003e\u003cp\u003edisassembly mechanism are known. Development of a potent inhibitor of the a-\u003c\/p\u003e\u003cp\u003eSNAP\/NSF mediated disassembly was carried out. Therefore, the SNARE motif of\u003c\/p\u003e\u003cp\u003eSynaptobrevin, one of the SNARE proteins, was used as a model system for the\u003c\/p\u003e\u003cp\u003einvestigation of defined SNARE\/SNAP complex recognition sites. The full length of the\u003c\/p\u003e\u003cp\u003eSNARE motif of Synaptobrevin was obtained using solid phase peptide synthesis.\u003c\/p\u003e\u003cp\u003eDifferent modifications at various residues within the sequence were introduced in\u003c\/p\u003e\u003cp\u003eorder to identify important interactions between a-SNAP and the SNARE complex and\u003c\/p\u003e\u003cp\u003eto prevent a-SNAP recognition.\u003c\/p\u003e\u003cp\u003eAdditionally, the regulator protein Complexin was synthesized as a ß-peptide analog,\u003c\/p\u003e\u003cp\u003ealso designed to inhibit the disassembly mechanism by preventing a-SNAP\u003c\/p\u003e\u003cp\u003erecognition through enhanced interaction between the ß-mimic and the\u003c\/p\u003e\u003cp\u003eSynaptobrevin and Syntaxin helices. By development of the Complexin ß-peptide\u003c\/p\u003e\u003cp\u003emimic as a 14-helix, the advantages of a well-defined secondary structure with high\u003c\/p\u003e\u003cp\u003ehelix propensity are obtained. Furthermore, the binding fragment of Complexin was\u003c\/p\u003e\u003cp\u003eperformed as a-peptide, extended with amino acids known to promote the a-helical\u003c\/p\u003e\u003cp\u003epropensity.\u003c\/p\u003e\u003cp\u003eFor understanding of biological systems the investigation of conformational dynamics\u003c\/p\u003e\u003cp\u003eand interactions of individual proteins is important. Therefore, in a final part, small\u003c\/p\u003e\u003cp\u003eindependently folding protein domains were synthesized by solid phase peptide\u003c\/p\u003e\u003cp\u003esynthesis and labeled with respect to the development of the single molecule\u003c\/p\u003e\u003cp\u003efluorescence spectroscopy (smFRET) technique. This method is a convenient tool of\u003c\/p\u003e\u003cp\u003emonitoring single folding and unfolding events of proteins.\u003c\/p\u003e\u003cdiv class=\"aw-variant-hidden-subtitle-div\" id=\"aw-variant-subtitle-9783869556628\"\u003e\u003ch3\u003e\u003c\/h3\u003e\u003c\/div\u003e","brand":"Libri","offers":[{"title":"Softcover - 9783869556628","offer_id":39463035043933,"sku":"9783869556628","price":33.0,"currency_code":"EUR","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0940\/0622\/files\/82667817-106f-4d95-b896-aa9a798b411a.jpg?v=1782454602","url":"https:\/\/shop.autorenwelt.de\/products\/design-and-synthesis-of-modified-snare-proteins-with-respect-to-the-a-snap-nsf-mediated-disassembly-von-annika-groschner","provider":"Autorenwelt Shop","version":"1.0","type":"link"}