2KO2

NOGO66

Summary for 2KO2

• Entry DOI: 10.2210/pdb2ko2/pdb
• Descriptor: Reticulon-4 (1 entity in total)
• Functional Keywords: nogo, membrane protein, peripheral, dpc micelle, myelin inhibitor, endoplasmic reticulum, membrane, phosphoprotein, transmembrane
• Biological source: Mus musculus (mouse)
• Cellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity): Q99P72
• Total number of polymer chains: 1
• Total formula weight: 9144.46

Authors

Cocco, M.J.,Schulz, J.,Vasudevan, S.V. (deposition date: 2009-09-08, release date: 2010-04-21, Last modification date: 2024-05-22)

Primary citation

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

Experimental method

SOLUTION NMR