2MP3

Truncated L126Z-sod1 in DPC micelle

2MP3 の概要

• エントリーDOI: 10.2210/pdb2mp3/pdb
• NMR情報: BMRB: 19962
• 分子名称: Superoxide dismutase [Cu-Zn] (1 entity in total)
• 機能のキーワード: l126z-sod1 mutant, dpc micelle, truncated, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P00441
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14039.51

構造登録者

Lim, L.,Song, J. (登録日: 2014-05-10, 公開日: 2015-05-20, 最終更新日: 2024-05-15)

主引用文献

Lim, L.,Lee, X.,Song, J.
Mechanism for transforming cytosolic SOD1 into integral membrane proteins of organelles by ALS-causing mutations
Biochim.Biophys.Acta, 1848:1-7, 2015

PubMed Abstract: Mutations in superoxide dismutase 1 (SOD1) cause familial amyotrophic lateral sclerosis (FALS), while wild-type SOD1 has been implicated in sporadic ALS (SALS). SOD1 mutants are now recognized to acquire one or more toxicities that include their association with mitochondrial and endoplasmic reticulum membranes but the underlying structural mechanism remains unknown. Here we determine NMR conformations of both wild-type and a truncation mutant (L126Z) of SOD1 in aqueous solution and a membrane environment. The truncation mutant (which causes FALS at very low levels, indicating its elevated toxicity) is highly unstructured in solution, failing to adopt the β-barrel SOD1 native structure. Wild-type SOD1 is also highly unstructured upon reduction of disulfides and depletion of zinc. Most remarkably, both mutant and wild type adopt similar, highly-helical conformations in a membrane environment. Thus, either truncation or depletion of zinc is sufficient to eliminate the native β-barrel structure, and transform cytosolic SOD1 into membrane proteins energetically driven by forming amphiphilic helices in membranes. That zinc-deficiency is sufficient to produce a similar transformation in wild-type SOD1 implies that the wild-type and FALS-linked SOD1 mutants may trigger ALS by a common mechanism.

PubMed: 25306968
DOI: 10.1016/j.bbamem.2014.10.002

実験手法

SOLUTION NMR