Structural insights into subunit-dependent functional regulation in epithelial sodium channels

被引：0
作者：
Houser, Alexandra [1 ]
Baconguis, Isabelle [2 ]
机构：
[1] Oregon Hlth & Sci Univ, Neurosci Grad Program, Portland, OR 97239 USA
[2] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA
来源：
STRUCTURE | 2025年 / 33卷 / 02期
基金：
美国国家科学基金会;
关键词：
NA+ CHANNEL; DELTA-SUBUNIT; GAMMA-SUBUNIT; CRYO-EM; BETA-ENAC; STRUCTURE VALIDATION; ELASTASE ACTIVATION; SERINE PROTEASES; ALPHA-SUBUNIT; EXPRESSION;
D O I：
10.1016/j.str.2024.11.013
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Epithelial sodium channels (ENaCs) play a crucial role in Na+ reabsorption in mammals. To date, four subunits have been identified-a, b, g, and d-believed to form different heteromeric complexes. Currently, only the structure of the abg complex is known. To investigate the formation of channels with different subunit compositions and to determine how each subunit contributes to distinct channel properties, we co-expressed human d, b, and g. Using single-particle cryoelectron microscopy, we observed three distinct ENaC complexes. The structures unveil a pattern in which b and g positions are conserved among the different complexes while the a position in abg trimer is occupied by either d or another b. The d subunit induces structural rearrangements in the g subunit, which may contribute to the differences in channel activity between abg and dbg channels. These structural changes provide molecular insights into how ENaC subunit composition modulates channel function.
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页码：349 / 362.e4
页数：19
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