7LK3

Crystal structure of untwinned human GABARAPL2

Summary for 7LK3

• Entry DOI: 10.2210/pdb7lk3/pdb
• Descriptor: Gamma-aminobutyric acid receptor-associated protein-like 2, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: autophagy, autophagosome, atg8 family, ubiquitin-like, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 28128.54

Authors

Scicluna, K.,Dewson, G.,Czabotar, P.E.,Birkinshaw, R.W. (deposition date: 2021-02-01, release date: 2021-05-12, Last modification date: 2023-10-18)

Primary citation

Scicluna, K.,Dewson, G.,Czabotar, P.E.,Birkinshaw, R.W.
A new crystal form of GABARAPL2.
Acta Crystallogr.,Sect.F, 77:140-147, 2021

PubMed Abstract: The Atg8 protein family comprises the GABA type A receptor-associated proteins (GABARAPs) and microtubule-associated protein 1 light chains 3 (MAP1LC3s) that are essential mediators of autophagy. The LC3-interacting region (LIR) motifs of autophagy receptors and adaptors bind Atg8 proteins to promote autophagosome formation, cargo recruitment, and autophagosome closure and fusion to lysosomes. A crystal structure of human GABARAPL2 has been published [PDB entry 4co7; Ma et al. (2015), Biochemistry, 54, 5469-5479]. This was crystallized in space group P2 with a monoclinic angle of 90° and shows a pseudomerohedral twinning pathology. This article reports a new, untwinned GABARAPL2 crystal form, also in space group P2, but with a 98° monoclinic angle. No major conformational differences were observed between the structures. In the structure described here, the C-terminal Phe117 binds into the LIR docking site (LDS) of a neighbouring molecule within the asymmetric unit, as observed in the previously reported structure. This crystal contact blocks the LDS for co-crystallization with ligands. Phe117 of GABARAPL2 is normally removed during biological processing by Atg4 family proteases. These data indicate that to establish interactions with the LIR, Phe117 should be removed to eliminate the crystal contact and liberate the LDS for co-crystallization with LIR peptides.

PubMed: 33949974
DOI: 10.1107/S2053230X21004489

Experimental method

X-RAY DIFFRACTION (1.9 Å)