Glycolipozyme membrane protein integrase (MPIase): recent data

Abstract

A novel factor for membrane protein integration, from the cytoplasmic membrane of Escherichia coli, named MPIase (membrane protein integrase), has recently been identified and characterized. MPIase was revealed to be essential for the membrane integration of a subset of membrane proteins, despite that such integration reactions have been, thus far, thought to occur spontaneously. The structure determination study revealed that MPIase is a novel glycolipid comprising a glycan chain with three N-acetylated amino sugars connected to diacylglycerol through a pyrophosphate linker. As MPIase catalyzes membrane protein integration, we propose that MPIase is a glycolipozyme on the basis of its enzyme-like function. The glycan chain exhibits a molecular chaperone-like function by directly interacting with substrate membrane proteins. Moreover, MPIase also affects the dimer structure of SecYEG, a translocon, thereby significantly stimulating preprotein translocation. The molecular mechanisms of MPIase functions will be outlined.

Biosynthesis of glycolipid MPIase (membrane protein integrase) is independent of the genes for ECA (enterobacterial common antigen)

“…MPIase (membrane protein integrase) is a glycolipid that drives membrane protein integration into the inner membrane of E. coli (Endo and Nishiyama, 2015;Nishiyama et al, 2006Nishiyama et al, , 2010Nishiyama et al, , 2012Nishiyama and Shimamoto, 2014). MPIase integrates a subset of membrane proteins of small size and, with a transmembrane domain at the C-terminus, leads us to propose the concept of 'glycolipozyme' (Nishiyama et al, 2012).…”

Cardiolipin is required in vivo for the stability of bacterial translocon and optimal membrane protein translocation and insertion

“…The SecB-preprotein complex is subsequently bound by SecA, a translocation ATPase, which also provides binding sites for preprotein mature domains 9 , anionic phospholipid 10 , SecYEG 11 as well as direct driving force for preprotein translocation through ATP binding and hydrolysis 11,12 . SecG stimulates protein translocation by undergoing a membrane topology inversion cycle 13 which is tightly coupled to its function and linked with the insertion-deinsertion cycle of SecA. Highly hydrophobic protein substrates are delivered to SecYEG cotranslationally via a pathway that requires their interaction with the prokaryotic signal recognition particle (Ffh) followed by formation of a RNC complex, which is targeted to the SecY-bound Ffh receptor FtsY 14,15 .…”

Novel translocation intermediate allows re‐evaluation of roles of ATP, proton motive force and SecG at the late stage of preprotein translocation

“…Later on, SecG inversion was found to absolutely require glycolipozyme MPIase [membrane protein integrase, (Endo & Nishiyama ; Nishiyama et al . , ; Nishiyama & Shimamoto )] (Moser et al . ).…”

“…Besides these proteinaceous factors, glycolipozyme MPIase (Nishiyama et al . , ; Nishiyama & Shimamoto ; Endo & Nishiyama ) has been shown to significantly stimulate preprotein translocation by modulating the dimer structure of SecYEG (Moser et al . ).…”