Research Progress on Bacterial Periplasmic Chaperone LolA

doi:10.13560/j.cnki.biotech.bull.1985.2020-1247

Abstract

Abstract:

Bacterial lipoprotein is a lipid-modified membrane protein,which participates in many important physiological processes such as cell membrane synthesis. The formation of lipoproteins depends on the Lol transport system. The protein is first synthesized in the form of precursors in the cytoplasm,and then processed into mature lipoproteins on the cell membrane and anchored to the perimembranous sides of bacteria. Lol system is composed of 5 proteins LolA-E,among which the lipoprotein is transported by the chaperone LolA in the periplasmic space. LolA transports the lipoprotein from LolCDE to LolB in the way of “mouth to mouth”,thereby completing the localization of lipoprotein. This review focuses on the structure,involved transport system and biological functions of periplasmic molecular chaperone LolA,aiming to provide more drug targets for the treatment of infectious diseases by understanding the molecular mechanism of lipoprotein transport.

Key words: bacterial lipoproteins, Lol transport system, periplasmic chaperone LolA, biological function

HE Xiao-li, GUO Lei-zhou, HAN Jia-hui, TANG Yin, YUAN Yuan, DAI Qi-lin, PING Shu-zhen, JIANG Shi-jie. Research Progress on Bacterial Periplasmic Chaperone LolA[J]. Biotechnology Bulletin, 2021, 37(8): 275-283.

Figures/Tables 5

Fig. 1 Crystal structure of Escherichia coli LolA[22] The hydrophobic cavity of LolA is composed of an open β-barrel and an α-helical lid,which is also a binding site for lipids;the C-terminal loop of LolA is composed of a short α-helix and a twelfth β-strand,which can correctly combine lipoprotein delivery to OM

Fig. 2 Lipoprotein transport and outer membrane anchoring mediated by the Lol system[22] a：Lipoprotein is first placed in LolE（1）,and then transferred to LolA located on LolC（2）. When LolCDE binds to lipoproteins,the interaction between LolA and LolCDE increases（solid arrow）. Then LolA forms a hydrophilic complex with lipoproteins in an ATP-dependent manner,and opens the hydrophobic cavity of LolA at the same time（3）. b：After passing through the periplasmic space,LolA and LolB interact in a “mouth to mouth” manner to transfer lipoproteins from LolA to LolB（4）,and finally locate to the outer membrane

Fig. 3 Crystal structure of LolA is combined with the periplasmic domain of LolC[30] A：The overall structure of the LolA-LolC complex. B：Interaction interface view. LolC and LolA are represented in cyan and gold,respectively. The residue belonging to Hook and Pad is shown in purple and orange. The content that interacts with LolC is displayed in a bar shape

Fig. 4 Transport model of lipoprotein on LolA and LolB[36] LolA and LolB are represented by green and blue barrels,respectively,and red represents the acyl chain. Step 1: a lipoprotein is obtained from LolCDE on the periplasmic side of the inner membrane. LolA undergoes a conformational change and adapts its hydrophobic cavity to 1 to 3 lipoprotein acyl chains. Step 2: the lipoprotein-LolA complex interacts with the LolB anchored on the outer membrane. In the complex,LolA and LolB form a hydrophobic,channel-like structure. Step 3: the acyl chain of the lipoprotein is transferred from LolA to LolB through the hydrophobic channel formed by these two proteins

Fig.5 Binding mode of BLP in the hydrophobic cavity of LolA[47] A：Left：Start configuration,where BLP（yellow）is located outside the LolA（cyan）cavity. Upper right：The combination of the three fat tails of BLP near the mouth of the cavity. Lower right：One fat tail is deep in the cavity,and the other two are at the mouth of the cavity. B：The minimum distance between the three independently simulated BLP fat tails and F90 residues（as shown in the illustration by Van der Waals notation）

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