Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER-Golgi interface.

ABSTRACT: ERp44 retrieves some endoplasmic reticulum (ER)-resident enzymes and immature oligomers of secretory proteins from the Golgi. Association of ERp44 with its clients is regulated by pH-dependent mechanisms, but the molecular details are not fully understood. Here we report high-resolution crystal structures of human ERp44 at neutral and weakly acidic pH. These structures reveal key regions in the C-terminal tail (C tail) missing in the original crystal structure, including a regulatory histidine-rich region and a subsequent extended loop. The former region forms a short α-helix (α16), generating a histidine-clustered site (His cluster). At low pH, the three Trx-like domains of ERp44 ("a," "b," and "b'") undergo significant rearrangements, likely induced by protonation of His157 located at th

SUBMITTER: Watanabe S 

PROVIDER: S-EPMC5402435 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature