5DCN

Crystal structure of LC3 in complex with TECPR2 LIR

Summary for 5DCN

• Entry DOI: 10.2210/pdb5dcn/pdb
• Descriptor: Microtubule-associated proteins 1A/1B light chain 3B, SULFATE ION (3 entities in total)
• Functional Keywords: lc3, autophagy, cell cycle
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm, cytoskeleton: Q9GZQ8
• Total number of polymer chains: 1
• Total formula weight: 15232.21

Authors

Stadel, D.,Huber, J.,Dotsch, V.,Rogov, V.V.,Behrends, C.,Akutsu, M. (deposition date: 2015-08-24, release date: 2016-03-09, Last modification date: 2024-05-08)

Primary citation

Stadel, D.,Millarte, V.,Tillmann, K.D.,Huber, J.,Tamin-Yecheskel, B.C.,Akutsu, M.,Demishtein, A.,Ben-Zeev, B.,Anikster, Y.,Perez, F.,Dotsch, V.,Elazar, Z.,Rogov, V.V.,Farhan, H.,Behrends, C.
TECPR2 Cooperates with LC3C to Regulate COPII-Dependent ER Export.
Mol.Cell, 60:89-104, 2015

PubMed Abstract: Hereditary spastic paraplegias (HSPs) are a diverse group of neurodegenerative diseases that are characterized by axonopathy of the corticospinal motor neurons. A mutation in the gene encoding for Tectonin β-propeller containing protein 2 (TECPR2) causes HSP that is complicated by neurological symptoms. While TECPR2 is a human ATG8 binding protein and positive regulator of autophagy, the exact function of TECPR2 is unknown. Here, we show that TECPR2 associates with several trafficking components, among them the COPII coat protein SEC24D. TECPR2 is required for stabilization of SEC24D protein levels, maintenance of functional ER exit sites (ERES), and efficient ER export in a manner dependent on binding to lipidated LC3C. TECPR2-deficient HSP patient cells display alterations in SEC24D abundance and ER export efficiency. Additionally, TECPR2 and LC3C are required for autophagosome formation, possibly through maintaining functional ERES. Collectively, these results reveal that TECPR2 functions as molecular scaffold linking early secretion pathway and autophagy.

PubMed: 26431026
DOI: 10.1016/j.molcel.2015.09.010

Experimental method

X-RAY DIFFRACTION (2 Å)