5GV3

Crystal structure of the membrane-distal domain of mouse lysosome-associated membrane protein 2 (LAMP-2)

Summary for 5GV3

• Entry DOI: 10.2210/pdb5gv3/pdb
• Related: 5GV0
• Descriptor: Lysosome-associated membrane glycoprotein 2, ZINC ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: membrane protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 40640.98

Authors

Tomabechi, Y.,Ehara, H.,Kukimoto-Niino, M.,Shirouzu, M. (deposition date: 2016-09-01, release date: 2017-09-06, Last modification date: 2024-10-09)

Primary citation

Terasawa, K.,Tomabechi, Y.,Ikeda, M.,Ehara, H.,Kukimoto-Niino, M.,Wakiyama, M.,Podyma-Inoue, K.A.,Rajapakshe, A.R.,Watabe, T.,Shirouzu, M.,Hara-Yokoyama, M.
Lysosome-associated membrane proteins-1 and -2 (LAMP-1 and LAMP-2) assemble via distinct modes.
Biochem. Biophys. Res. Commun., 479:489-495, 2016

PubMed Abstract: Lysosome-associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2) have a large, heavily glycosylated luminal domain composed of two subdomains, and are the most abundant protein components in lysosome membranes. LAMP-1 and LAMP-2 have distinct functions, and the presence of both proteins together is required for the essential regulation of autophagy to avoid embryonic lethality. However, the structural aspects of LAMP-1 and LAMP-2 have not been elucidated. In the present study, we demonstrated that the subdomains of LAMP-1 and LAMP-2 adopt the unique β-prism fold, similar to the domain structure of the dendritic cell-specific-LAMP (DC-LAMP, LAMP-3), confirming the conserved aspect of this family of lysosome-associated membrane proteins. Furthermore, we evaluated the effects of the N-domain truncation of LAMP-1 or LAMP-2 on the assembly of LAMPs, based on immunoprecipitation experiments. We found that the N-domain of LAMP-1 is necessary, whereas that of LAMP-2 is repressive, for the organization of a multimeric assembly of LAMPs. Accordingly, the present study suggests for the first time that the assembly modes of LAMP-1 and LAMP-2 are different, which may underlie their distinct functions.

PubMed: 27663661
DOI: 10.1016/j.bbrc.2016.09.093

Experimental method

X-RAY DIFFRACTION (2.096 Å)