5LM2: Crystal Structure Of Hd-ptp Phosphatase

Endosomal sorting complexes required for transport (ESCRTs) are essential for ubiquitin-dependent degradation of mitogenic receptors, a process often compromised in cancer pathologies. Sorting of ubiquinated receptors via ESCRTs is controlled by the tumor suppressor phosphatase HD-PTP. The specific interaction between HD-PTP and the ESCRT-I subunit UBAP1 is critical for degradation of growth factor receptors and integrins. Here, we present the structural characterization by X-ray crystallography and double electron-electron resonance spectroscopy of the coiled-coil domain of HD-PTP and its complex with UBAP1. The coiled-coil domain adopts an unexpected open and rigid conformation that contrasts with the closed and flexible coiled-coil domain of the related ESCRT regulator Alix. The HD-PTP:UBAP1 structure identifies the molecular determinants of the interaction and provides a molecular basis for the specific functional cooperation between HD-PTP and UBAP1. Our findings provide insights into the molecular mechanisms of regulation of ESCRT pathways that could be relevant to anticancer therapies.
PDB ID: 5LM2Download
MMDB ID: 145281
PDB Deposition Date: 2016/7/28
Updated in MMDB: 2016/12
Experimental Method:
x-ray diffraction
Resolution: 2.54  Å
Source Organism:
Similar Structures:
Biological Unit for 5LM2: monomeric; determined by author
Molecular Components in 5LM2
Label Count Molecule
Protein (1 molecule)
Tyrosine-protein Phosphatase Non-receptor Type 23(Gene symbol: PTPN23)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB