The Effects of Mgr2 on Hydrophobicity Threshold for Transmembrane Helix Insertion into the Mitochondrial Inner Membrane

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Yoo, Suji; Lee, Seoun; Kim, Hyun

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Biophysical Society
Biophysical Society 61st Annual Meeting, pp. 11-11
The Effects of Mgr2 on Hydrophobicity Threshold for Transmembrane Helix Insertion into the Mitochondrial Inner Membrane자연과학
The majority of integral membrane proteins have tightly packed α-helical transmembrane segment (TMS). The formation of an α-helix and overall hydrophobicity are crucial determinants for translocon-mediated recognition and insertion of a TMS into the lipid bilayer, involving direct interaction between TMS and the surrounding lipid.
While overall hydrophobicity required for TMS insertion into the mitochondrial inner membrane (MIM) is shown comparable to what is required in the endoplasmic reticulum membrane, differences in threshold hydrophobicity and effects of flanking charged residues have been observed (Botelho et al., EMBO J, 2011). What contributes these differences is currently unknown. The TIM23 complex is the main channel for import and inner membrane insertion of presequence containing proteins. The recently identified subunit of TIM23 complex, Mgr2 is reported to act as a lateral gatekeeper to MIM proteins; absence of Mgr2 facilitates membrane insertion while overexpression delays (Ieva et al., Molecular Cell, 2014). This led us to hypothesize that Mgr2 may play a role in screening TMS for membrane insertion. To test this idea, present study has undertaken to systematically determine the effects of Mgr2 on the TIM23-mediated TM helix insertion.
By replacing the 1st TM of Mgm1 with 19 amino acid stretch composed of n leucines and 19-n alanines (from 1L to 8L), we analyzed membrane insertion efficiency of Leu/Ala segments of various hydrophobicity. The relative amounts of l-Mgm1 (which is the 1st TM inserted form) increased with higher number of leucines. While 50% membrane insertion reached for n≒5-6 in WT, this hydrophobicity threshold is decreased to n≒4-5 when Mgr2 was deleted and increased to n≒6 upon overexpression of Mgr2. These data suggest that Mgr2 is involved in modulating the TM helix insertion efficiency in the mitochondrial inner membrane.
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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