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Publication Abstract from PubMed

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 beta-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.

Lysosome-associated membrane proteins-1 and -2 (LAMP-1 and LAMP-2) assemble via distinct modes.,Terasawa K, Tomabechi Y, Ikeda M, Ehara H, Kukimoto-Niino M, Wakiyama M, Podyma-Inoue KA, Rajapakshe AR, Watabe T, Shirouzu M, Hara-Yokoyama M Biochem Biophys Res Commun. 2016 Oct 21;479(3):489-495. doi:, 10.1016/j.bbrc.2016.09.093. Epub 2016 Sep 20. PMID:27663661^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.