Clustered hydrophobic amino acids in amphipathic helices mediate erlin1/2 complex assembly.
Clustered hydrophobic amino acids in amphipathic helices mediate erlin1/2 complex assembly.
复制标题
两亲性螺旋中的簇状疏水性氨基酸介导 erlin1/2 复合物组装。
DOI：
10.1016/j.bbrc.2011.10.032
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发表时间：
2011
影响因子：
3.1
通讯作者：
Wojcikiewicz,RichardJH
中科院分区：
文献类型：
--
作者：
Pednekar,Deepa;Wang,Yuan;Fedotova,TatyanaV;Wojcikiewicz,RichardJH
Erlin1 and erlin2 are highly homologous, ∼40kDa, endoplasmic reticulum membrane proteins that assemble into a ring-shaped complex with a mass of ∼2MDa. How this complex is formed is not understood, but appears to involve multiple interactions, including a coiled-coil region that mediates lower-order erlin assembly, and a short hydrophobic region, termed the “assembly domain”, that mediates higher-order assembly into ∼2MDa complexes. Here we have used molecular modeling, mutagenesis and cross-linking to examine the role of the assembly domain in higher-order assembly. We find (i) that the assembly domains of erlin1 and erlin2 are amphipathic helices, (ii) that erlin1 alone and erlin2 alone can assemble into ∼2MDa complexes, (iii) that higher-order assembly is strongly inhibited by point mutations to the assembly domain, (iv) that three interacting hydrophobic residues in the assembly domain and aromaticity are essential for higher-order assembly, and (iv) that while erlins1 and 2 are equally capable of forming lower-order homo- and hetero-oligomers, hetero-oligomers are the most prevalent form when erlin1 and erlin2 are co-expressed. Overall, we conclude that the ∼2MDa erlin1/2 complex is composed of an assemblage of lower-order hetero-oligomers, probably heterotrimers, linked together by assembly domain hydrophobic residues.
