6JVB

Crystal Structure of Human CRMP2 1-532, AGE-modified

6JVB の概要

• エントリーDOI: 10.2210/pdb6jvb/pdb
• 分子名称: Dihydropyrimidinase-related protein 2 (2 entities in total)
• 機能のキーワード: microtubule associated protein, gap activity, neuronal protein, structural protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 237039.92

構造登録者

Jiang, X.,Ogawa, T.,Hirokawa, N. (登録日: 2019-04-16, 公開日: 2019-10-09, 最終更新日: 2023-11-22)

主引用文献

Toyoshima, M.,Jiang, X.,Ogawa, T.,Ohnishi, T.,Yoshihara, S.,Balan, S.,Yoshikawa, T.,Hirokawa, N.
Enhanced carbonyl stress induces irreversible multimerization of CRMP2 in schizophrenia pathogenesis.
Life Sci Alliance, 2:-, 2019

PubMed Abstract: Enhanced carbonyl stress underlies a subset of schizophrenia, but its causal effects remain elusive. Here, we elucidated the molecular mechanism underlying the effects of carbonyl stress in iPS cells in which the gene encoding zinc metalloenzyme glyoxalase I (), a crucial enzyme for the clearance of carbonyl stress, was disrupted. The iPS cells exhibited significant cellular and developmental deficits, and hyper-carbonylation of collapsing response mediator protein 2 (CRMP2). Structural and biochemical analyses revealed an array of multiple carbonylation sites in the functional motifs of CRMP2, particularly D-hook (for dimerization) and T-site (for tetramerization), which are critical for the activity of the CRMP2 tetramer. Interestingly, carbonylated CRMP2 was stacked in the multimer conformation by irreversible cross-linking, resulting in loss of its unique function to bundle microtubules. Thus, the present study revealed that the enhanced carbonyl stress stemmed from the genetic aberrations results in neurodevelopmental deficits through the formation of irreversible dysfunctional multimer of carbonylated CRMP2.

PubMed: 31591136
DOI: 10.26508/lsa.201900478

実験手法

X-RAY DIFFRACTION (2 Å)