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Crystal structure of human ERp44 shows a dynamic functional modulation by its carboxy‐terminal tail
Author(s) -
Wang Likun,
Wang Lei,
Vavassori Stefano,
Li Shengjian,
Ke Huimin,
Anelli Tiziana,
Degano Massimo,
Ronzoni Riccardo,
Sitia Roberto,
Sun Fei,
Wang Chihchen
Publication year - 2008
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2008.88
Subject(s) - terminal (telecommunication) , modulation (music) , chemistry , microbiology and biotechnology , computer science , biophysics , biology , physics , computer network , acoustics
ERp44 mediates thiol‐dependent retention in the early secretory pathway, forming mixed disulphides with substrate proteins through its conserved CRFS motif. Here, we present its crystal structure at a resolution of 2.6 Å. Three thioredoxin domains—a, b and b′—are arranged in a clover‐like structure. A flexible carboxy‐terminal tail turns back to the b′ and a domains, shielding a hydrophobic pocket in domain b′ and a hydrophobic patch around the CRFS motif in domain a. Mutational and functional studies indicate that the C‐terminal tail gates the CRFS area and the adjacent hydrophobic pocket, dynamically regulating protein quality control.