2w50

N-terminal domain of human conserved dopamine neurotrophic factor (CDNF)

spinqualitylabelsall models 2w50, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2w50 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CDNF_HUMAN] Trophic factor for dopamine neurons. Prevents the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons. When administered after 6-OHDA-lesioning, restores the dopaminergic function and prevents the degeneration of dopaminergic neurons in substantia nigra (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. The structure of the conserved neurotrophic factors MANF and CDNF explains why they are bifunctional.,Parkash V, Lindholm P, Peranen J, Kalkkinen N, Oksanen E, Saarma M, Leppanen VM, Goldman A Protein Eng Des Sel. 2009 Apr;22(4):233-41. Epub 2009 Mar 3. PMID:19258449 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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