GRP78 protects a disintegrin and metalloprotease 17 against protein-disulfide isomerase A6 catalyzed inactivation

Autor(es):Mostrar menos -

Schaefer, Miriam ^[1] ; Granato, Daniela C. ^[2] ; Krossa, Sebastian ^[3] ; Bartels, Anne-Kathrin ^[1] ; Yokoo, Sami ^[2] ; Dusterhoft, Stefan ^[4] ; Koudelka, Tomas ^[5] ; Scheidig, Axel J. ^[3] ; Tholey, Andreas ^[5] ; Paes Leme, Adriana F. ^[2] ; Groetzinger, Joachim ^[1] ; Lorenzen, Inken ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Univ Kiel, Inst Biochem, Olshausenstr 40, D-24118 Kiel - Germany

^[2] CNPEM, LNBio, Lab Nacl Biociencias, Lab Espectrometria Massas, BR-13083970 Campinas, SP - Brazil

^[3] Inst Zool, Dept Biol Struct, Kiel - Germany

^[4] Sir William Dunn Sch Pathol, Oxford - England

^[5] Univ Kiel, Inst Expt Med, Div Systemat Proteome Res, Kiel - Germany

• Tipo de documento: Artigo Científico
• Fonte: FEBS Letters; v. 591, n. 21, p. 3567-3587, NOV 2017.
• Citações Web of Science: 4

Resumo

The shedding of ectodomains is a crucial mechanism in many physiological and pathological events. A disintegrin and metalloprotease-17 (ADAM17) is a key sheddase involved in essential processes, such as development, regeneration, and immune defense. ADAM17 exists in two conformations which differ in their disulfide connection in the membrane-proximal domain (MPD). Protein-disulfide isomerases (PDIs) on the cell surface convert the open MPD into a rigid closed form, which corresponds to inactive ADAM17. ADAM17 is expressed in its open activatable form in the endoplasmic reticulum (ER) and consequently must be protected against ER-resident PDI activity. Here, we show that the chaperone 78-kDa glucose-regulated protein (GRP78) protects the MPD against PDI-dependent disulfide-bond isomerization by binding to this domain and, thereby, preventing ADAM17 inhibition. (AU)

• Processo FAPESP: 09/54067-3 - EMU: aquisição de um espectrômetro de massas acoplado a cromatografia líquida para permitir ampliar a capacidade de atendimento de usuários e disponibilizar novas tecnologias no Laboratório de Espectrometria de Massas do Centro de Biologia Molecular Estrutural (ABTLUS)
• Beneficiário: Adriana Franco Paes Leme
• Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 11/02267-9 - Busca de ligantes e Mapeamento dos domínios da ADAM-17 responsáveis pela interação com os ligantes.
• Beneficiário: Daniela Campos Granato
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 10/19278-0 - Estudo da regulação de ADAMs em câncer oral
• Beneficiário: Adriana Franco Paes Leme
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores