8YAD

structure of SPG11-SPG15 complex

Summary for 8YAD

• Entry DOI: 10.2210/pdb8yad/pdb
• EMDB information: 39094 39096
• Descriptor: Spatacsin, Zinc finger FYVE domain-containing protein 26 (2 entities in total)
• Functional Keywords: complex, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 564126.50

Authors

Su, M.-Y. (deposition date: 2024-02-08, release date: 2025-03-26, Last modification date: 2025-04-16)

Primary citation

Mai, X.,Wang, Y.,Wang, X.,Liu, M.,Teng, F.,Liu, Z.,Su, M.Y.,Stjepanovic, G.
Structural basis for membrane remodeling by the AP5-SPG11-SPG15 complex.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: The human spastizin (spastic paraplegia 15, SPG15) and spatacsin (spastic paraplegia 11, SPG11) complex is involved in the formation of lysosomes, and mutations in these two proteins are linked with hereditary autosomal-recessive spastic paraplegia. SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes. We employed cryogenic-electron microscopy and in silico predictions to investigate the structural assemblies of the SPG11-SPG15 and AP5-SPG11-SPG15 complexes. The W-shaped SPG11-SPG15 intertwined in a head-to-head fashion, and the N-terminal region of SPG11 is required for AP5 complex interaction and assembly. The AP5 complex is in a super-open conformation. Our findings reveal that the AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro. These studies provide insights into the structure and function of the spastic paraplegia AP5-SPG11-SPG15 complex, which is essential for the initiation of autolysosome tubulation.

PubMed: 40175557
DOI: 10.1038/s41594-025-01500-0

Experimental method

ELECTRON MICROSCOPY (4.02 Å)