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GRP 78 protects a disintegrin and metalloprotease 17 against protein‐disulfide isomerase A6 catalyzed inactivation
Author(s) -
Schäfer Miriam,
Granato Daniela C.,
Krossa Sebastian,
Bartels AnneKathrin,
Yokoo Sami,
Düsterhöft Stefan,
Koudelka Tomas,
Scheidig Axel J.,
Tholey Andreas,
Paes Leme Adriana F.,
Grötzinger Joachim,
Lorenzen Inken
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12858
Subject(s) - disintegrin , endoplasmic reticulum , metalloproteinase , chemistry , protein disulfide isomerase , chaperone (clinical) , microbiology and biotechnology , isomerase , protein folding , biochemistry , enzyme , biology , medicine , pathology
The shedding of ectodomains is a crucial mechanism in many physiological and pathological events. A disintegrin and metalloprotease‐17 ( ADAM 17) is a key sheddase involved in essential processes, such as development, regeneration, and immune defense. ADAM 17 exists in two conformations which differ in their disulfide connection in the membrane‐proximal domain ( MPD ). Protein‐disulfide isomerases ( PDI s) on the cell surface convert the open MPD into a rigid closed form, which corresponds to inactive ADAM 17. ADAM 17 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‐ kD a glucose‐regulated protein ( GRP 78) protects the MPD against PDI ‐dependent disulfide‐bond isomerization by binding to this domain and, thereby, preventing ADAM 17 inhibition.