Structural study of the HD-PTP Bro1 domain in a complex with the core region of STAM2, a subunit of ESCRT-0
Cited 12 time in
- Structural study of the HD-PTP Bro1 domain in a complex with the core region of STAM2, a subunit of ESCRT-0
- Juhyun Lee; Kyoung Jin Oh; Dasom Lee; Bo Yeon Kim; J S Choi; Bonsu Ku; Seung Jun Kim
- Bibliographic Citation
- PLoS One, vol. 11, no. 2, pp. e0149113-e0149113
- Publication Year
- EGFR is a key player in cell proliferation and survival signaling, and its sorting into MVBs for eventual lysosomal degradation is controlled by the coordination of multiple ESCRT complexes on the endosomal membrane. HD-PTP is a cytosolic protein tyrosine phosphatase, and is associated with EGFR trafficking by interacting with the ESCRT-0 protein STAM2 and the ESCRT-III protein CHMP4B via its N-terminal Bro1 domain. Intriguingly, the homologous domain of two other human Bro1 domain-containing proteins, Alix and Brox, binds CHMP4B but not STAM2, despite their high structural similarity. To elucidate this binding specificity, we determined the complex structure of the HD-PTP Bro1 domain bound to the STAM2 core region. STAM2 binds to the hydrophobic concave pocket of the HD-PTP Bro1 domain, as CHMP4B does to the pocket of Alix, Brox, or HD-PTP but in the opposite direction. Critically, Thr145 of HD-PTP, corresponding to Lys151 of Alix and Arg145 of Brox, is revealed to be a determinant residue enabling this protein to bind STAM2, as the Alix- or Brox-mimicking mutations of this residue blocks the intermolecular interaction. This work therefore provides the structural basis for how HD-PTP recognizes the ESCRT-0 component to control EGFR sorting.
- Public Library of Science
- Appears in Collections:
- Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Ochang Branch Institute > Anticancer Agent Research Center > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
- Files in This Item:
Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.