Download MendeleyLysosome-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, K.A., Rajapakshe, A.R., Watabe, T., Shirouzu, M., Hara-Yokoyama, M.(2016) Biochem Biophys Res Commun 479: 489-495
- PubMed: 27663661
- DOI: https://doi.org/10.1016/j.bbrc.2016.09.093
- Primary Citation of Related Structures:
5GV0, 5GV3 - 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.
Organizational Affiliation:
Department of Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan.
