2W51

Human mesencephalic astrocyte-derived neurotrophic factor (MANF)

2W51 の概要

• エントリーDOI: 10.2210/pdb2w51/pdb
• 関連するPDBエントリー: 2W50
• 分子名称: PROTEIN ARMET (1 entity in total)
• 機能のキーワード: manf, cdnf, saposin, secreted, er stress, phosphoprotein, neurotrophic factor, sialic acid, glycoprotein, growth factor, hormone
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18195.14

構造登録者

Parkash, V.,Lindholm, P.,Peranen, J.,Kalkkinen, N.,Oksanen, E.,Saarma, M.,Leppanen, V.M.,Goldman, A. (登録日: 2008-12-03, 公開日: 2009-03-17, 最終更新日: 2024-11-13)

主引用文献

Parkash, V.,Lindholm, P.,Peranen, J.,Kalkkinen, N.,Oksanen, E.,Saarma, M.,Leppanen, V.M.,Goldman, A.
The Structure of the Conserved Neurotrophic Factors Manf and Cdnf Explains Why They are Bifunctional.
Protein Eng.Des.Sel., 22:233-241, 2009

PubMed Abstract: We have solved the structures of mammalian mesencephalic astrocyte-derived neurotrophic factor (MANF) and conserved dopamine neurotrophic factor (CDNF). CDNF protects and repairs midbrain dopaminergic neurons in vivo; MANF supports their survival in culture and is also cytoprotective against endoplasmic reticulum (ER) stress. Neither protein structure resembles any known growth factor but the N-terminal domain is a saposin-like lipid-binding domain. MANF and CDNF may thus bind lipids or membranes. Consistent with this, there are two patches of conserved lysines and arginines. The natively unfolded MANF C-terminus contains a CKGC disulphide bridge, such as reductases and disulphide isomerases, consistent with a role in ER stress response. The structure thus explains why MANF and CDNF are bifunctional; neurotrophic activity may reside in the N-terminal domain and ER stress response in the C-terminal domain. Finally, we identified three changes, (MANF)I10-->K(CDNF), (MANF)E79-->M(CDNF) and (MANF)K88-->L(CDNF), that may account for the biological differences between the proteins.

PubMed: 19258449
DOI: 10.1093/PROTEIN/GZN080

実験手法

X-RAY DIFFRACTION (2.8 Å)