2KO2

NOGO66

2KO2 の概要

• エントリーDOI: 10.2210/pdb2ko2/pdb
• 分子名称: Reticulon-4 (1 entity in total)
• 機能のキーワード: nogo, membrane protein, peripheral, dpc micelle, myelin inhibitor, endoplasmic reticulum, membrane, phosphoprotein, transmembrane
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity): Q99P72
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9144.46

構造登録者

Cocco, M.J.,Schulz, J.,Vasudevan, S.V. (登録日: 2009-09-08, 公開日: 2010-04-21, 最終更新日: 2024-05-22)

主引用文献

Vasudevan, S.V.,Schulz, J.,Zhou, C.,Cocco, M.J.
Protein folding at the membrane interface, the structure of Nogo-66 requires interactions with a phosphocholine surface.
Proc.Natl.Acad.Sci.USA, 107:6847-6851, 2010

PubMed Abstract: Repair of damage to the central nervous system (CNS) is inhibited by the presence of myelin proteins that prevent axonal regrowth. Consequently, growth inhibitors and their common receptor have been identified as targets in the treatment of injury to the CNS. Here we describe the structure of the extracellular domain of the neurite outgrowth inhibitor (Nogo) in a membrane-like environment. Isoforms of Nogo are expressed with a common C terminus containing two transmembrane (TM) helices. The ectodomain between the two TM helices, Nogo-66, is active in preventing axonal growth [GrandPre T, Nakamura F, Vartanian T, Strittmatter SM (2000) Nature 403:439-444]. We studied the structure of Nogo-66 alone and in the presence of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles and dodecylphosphocholine (DPC) micelles as membrane mimetics. We find that Nogo-66 is largely disordered when free in solution. However, when bound to a phosphocholine surface Nogo-66 adopts a unique, stable fold, even in the absence of TM anchors. Using paramagnetic probes and protein-DPC nuclear Overhauser effects (NOEs), we define portions of the growth inhibitor likely to be accessible on the cell surface. With these data we predict that residues (28-58) are available to bind the Nogo receptor, which is entirely consistent with functional assays. Moreover, the conformations and relative positions of side chains recognized by the receptor are now defined and provide a foundation for antagonist design.

PubMed: 20351248
DOI: 10.1073/pnas.0911817107

実験手法

SOLUTION NMR