5YZ5

Crystal Structure of Human CRMP-2 with T509D-T514D-S518D-S522D mutations

5YZ5 の概要

• エントリーDOI: 10.2210/pdb5yz5/pdb
• 関連するPDBエントリー: 5X1A 5X1C 5X1D
• 分子名称: Dihydropyrimidinase-related protein 2, SULFATE ION (3 entities in total)
• 機能のキーワード: developmental protein, phosphoprotein, microtubule associated proteins, neurogenesis, dihydropyrimidase-related protein, collapsin response mediator protein, protein binding, cytosolic protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm, cytosol : Q16555
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57563.90

構造登録者

Imasaki, T.,Sumi, T.,Aoki, M.,Sakai, N.,Nitta, E.,Shirouzu, M.,Nitta, R. (登録日: 2017-12-13, 公開日: 2018-03-21, 最終更新日: 2024-03-27)

主引用文献

Sumi, T.,Imasaki, T.,Aoki, M.,Sakai, N.,Nitta, E.,Shirouzu, M.,Nitta, R.
Structural Insights into the Altering Function of CRMP2 by Phosphorylation.
Cell Struct. Funct., 43:15-23, 2018

PubMed Abstract: Collapsin response mediator protein 2 (CRMP2) regulates neuronal polarity by controlling microtubule dynamics. CRMP2 activity is regulated by semaphorin-induced phosphorylation at the C-terminal tail domain. Unphosphorylated CRMP2 induces effective axonal microtubule formation to give the axonal characteristics to a neurite, whereas phosphorylated CRMP2 leads to the apparently opposite effect, growth cone collapse. We have recently characterized the structural detail of CRMP2-induced axonal microtubule formation (Niwa et al. (2017) Sci. Rep., 7: 10681). CRMP2 forms the hetero-trimer with GTP-tubulin to induce effective axonal microtubule formation in the future axon. Phosphorylation of CRMP2 has been reported to decrease the affinity between CRMP2 and the microtubule, albeit the molecular mechanisms of how the phosphorylation of CRMP2 changes the structure to achieve distinct effects from unphosphorylated CRMP2 is not well understood. Here we performed a series of biochemical and structural analyses of phospho-mimic CRMP2. Phosphorylation of CRMP2 undergoes small conformational changes at the C-terminal tail with shifting the surface charge, which not only alters the interactions within the CRMP2 tetramer but also alters the interactions with GTP-tubulin. Consequently, phospho-mimic CRMP2 fails to form a hetero-trimer with GTP-tubulin, thus losing the ability to establish and maintain the axonal microtubules.Key words: CRMP2, phosphorylation, microtubule, axon, crystal structure.

PubMed: 29479005
DOI: 10.1247/csf.17025

実験手法

X-RAY DIFFRACTION (1.8 Å)