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Structural and Functional Studies of the Protein Degradation Complex
Author(s) -
Zhao Gang,
Li Guangtao,
Zhou Xiaoke,
Schindelin Hermann,
Lennarz William J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1005.2
Subject(s) - endoplasmic reticulum associated protein degradation , endoplasmic reticulum , biochemistry , glycoprotein , cytoplasm , microbiology and biotechnology , chemistry , pngase f , cytosol , golgi apparatus , protein folding , aaa proteins , biology , glycan , atpase , unfolded protein response , enzyme
In eukaryotes, the endoplasmic reticulum associated degradation (ERAD) pathway plays an important role in the degradation of misfolded glycoproteins. Using functional and biochemical techniques we identified a higher order protein complex consisting of two ER membrane proteins, Derlin1 and gp78, and the cytoplasmic proteins p97/VCP, peptide:N‐glycanase (PNGase) and HR23. This complex may assist the retro‐translocation process and subsequently escort misfolded glycoproteins to the proteasome for degradation. The multifunctional AAA‐ATPase p97 is believed to extract ERAD substrates through the retrotranslocon and, by association with various cofactors, recruit and process the ubiquitinated substrates. One of the p97 binding proteins is the cytosolic PNGase, which hydrolytically removes the N‐linked glycan chains from denatured glycoproteins. Recently, we found a novel binding motif in the C‐terminal of mouse p97, which mediates the binding of p97 to PNGase and other substrate‐processing cofactors. The crystal structure of the N‐terminal domain of mouse PNGase in complex with this motif demonstrates the pivotal role of the penultimate tyrosine residue of p97 in its interaction with PNGase.