{"id":6304,"date":"2023-02-17T07:13:03","date_gmt":"2023-02-17T07:13:03","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2019-development-of-photocrosslinking-probes-based-on-huwentoxin-iv-to-map-the-site-of-interaction-on-nav1-7\/"},"modified":"2023-02-17T07:13:04","modified_gmt":"2023-02-17T07:13:04","slug":"2019-development-of-photocrosslinking-probes-based-on-huwentoxin-iv-to-map-the-site-of-interaction-on-nav1-7","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2019-development-of-photocrosslinking-probes-based-on-huwentoxin-iv-to-map-the-site-of-interaction-on-nav1-7\/","title":{"rendered":"2019 &#8211; Development of Photocrosslinking Probes Based on Huwentoxin-IV to Map the Site of Interaction on NaV1.7"},"content":{"rendered":"<p>Highlights:\u00a0Development of six potent diazirine-containing photoprobes based on Huwentoxin-IV. Photoprobes specifically photolabel purified bacterial-NaV1.7 VSD2 chimeric channels. Proteomic mass spectrometry identifies binding site on S1-S2 loop and S3 helix. Proposed model of HwTx-IV binding reveals importance of K27 and R29. Summary:\u00a0Voltage-gated sodium (NaV) channels respond to changes in the membrane potential of excitable cells through the concerted action of four voltage-sensor domains (VSDs). Subtype NaV1.7 plays an important role in the propagation of signals in pain-sensing neurons and is a target for the clinical development of novel analgesics. Certain inhibitory cystine knot (ICK) peptides produced by venomous animals potently modulate NaV1.7; however, the molecular mechanisms underlying their selective binding and activity remain elusive. This study reports on the design of a library of photoprobes based on the potent spider toxin Huwentoxin-IV and the determination of the toxin binding interface on VSD2 of NaV1.7 through a photocrosslinking and tandem mass spectrometry approach. Our Huwentoxin-IV probes selectively crosslink to extracellular loop S1-S2 and helix S3 of VSD2 in a chimeric channel system. Our results provide a strategy that will enable mapping of sites of interaction of other ICK peptides on NaV channels.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50,76],"therapeutic_areas":[56],"target_categories":[61],"target_families":[332],"targets":[116],"resource_keyword":[],"class_list":["post-6304","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","therapeutic_areas-pain","target_categories-voltage-gated-ion-channels","target_families-nav-channels","targets-nav1-7"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6304","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=6304"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6304"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6304"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6304"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6304"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6304"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6304"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6304"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6304"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}