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Institute of Molecular and Cellular Biosciences
The University of Tokyo
Laboratory of Cell Biogenesis

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htokuda@iam.u-tokyo.ac.jp
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Tel: +81-3-5841-7830〜7833　　Fax: +81-3-3-5841-8464

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　Proteins must be localized at their final destinations to exert their physiological functions. On the way to their destinations, many proteins cross biological membranes. A number of factors are involved in protein translocation across biological membranes and protein localization in specific cellular compartments. Escherichia coli consists of four compartments, the cytoplasm, inner (cytoplasmic) membrane, periplasm and outer membrane (Fig. 1). Proteins destined for the periplasm and outer membrane are synthesized as precursors and then translocated across the cytoplasmic membrane by the machinery comprising Sec factors. The sorting and transport of translocated proteins then take place, leading to their localization at the final destination. Lipoproteins possess the N-terminal cysteine residue modified with fatty acids and are localized on either the inner or outer membrane depending on their sorting signals (Fig. 2).
Fig.1Fig.2

We have discovered a LolCDE complex that releases outer membrane-specific lipoproteins from the inner membrane, a periplasmic molecular chaperone LolA that forms a complex with lipoproteins, and an outer membrane receptor LolB. Outline of the mechanism underlying the lipoprotein sorting has been thus revealed (Fig. 3). Despite their dissimilar amino acid sequences, the structures of LolA and LolB are strikingly similar to each other. The LolCDE complex belongs to the ABC transporter super family but catalyses a unique function, i.e. the release of lipoproteins from the outer leaflet of membranes.　　　　　　　　　　　→ Click !!

　It is not known how phospholipids are transferred from the inner to the outer membrane. Moreover, little is known how proteins are inserted into the inner membrane and then transferred to lipid bilayer to form a final topology. We are also trying to reveal these mechanisms to understand how E. coli cell envelope is formed.