8OQH

Structure of the cytosolic domain of lysosome-associated TMEM55B

Summary for 8OQH

• Entry DOI: 10.2210/pdb8oqh/pdb
• Descriptor: Type 1 phosphatidylinositol 4,5-bisphosphate 4-phosphatase, ZINC ION (3 entities in total)
• Functional Keywords: membrane trafficking, lysosomes, jip4, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 19882.96

Authors

Waschbusch, D.,Khan, A.R. (deposition date: 2023-04-12, release date: 2023-11-29, Last modification date: 2026-03-04)

Primary citation

Waschbusch, D.,Pal, P.,Nirujogi, R.S.,Cavin, M.,Singh, J.,Alessi, D.R.,Khan, A.R.
Structural basis for binding of RILPL1 to TMEM55B reveals a lysosomal platform for adaptor assembly through a conserved peptide motif.
Structure, 34:296-310.e5, 2026

PubMed Abstract: Inherited mutations in VPS35 and LRRK2 kinase lead to hyperphosphorylation of Rab GTPases. RH2 domain-containing proteins from the RILP homology family, such as RILPL1, are Rab effectors that recognize the LRRK2-phosphorylated switch 2 threonine of phospho-Rab8A and phospho-Rab10. Phospho-Rabs are also seen on lysosomal membranes in complex with RILPL1 and TMEM55B, a 284-residue lysosomal membrane protein lacking homology to known proteins. Here, we report crystal structures of the cytosolic region 80-166 of TMEM55B alone and in complex with a C-terminal RILPL1 peptide, which we define as the TMEM55B-binding motif (TBM). The RILPL1 TBM sits in a shallow groove across two tandem RING-like domains of TMEM55B, each forming a Zn-stabilized 40-residue β-sandwich. Co-immunoprecipitation and mass spectrometry studies indicate that TMEM55B forms complexes independently of phospho-Rabs with conserved TBMs found in JIP3, JIP4, OCRL, WDR81, and TBC1D9B. These studies suggest that TMEM55B acts as a central hub for adaptor recruitment on lysosomes.

PubMed: 41314214
DOI: 10.1016/j.str.2025.11.003

Experimental method

X-RAY DIFFRACTION (1.76 Å)