Sandbox Reserved 938
From Proteopedia
| Line 17: | Line 17: | ||
===N-terminal domain=== | ===N-terminal domain=== | ||
| - | Here is the <scene name='57/579708/N_zoom_rainbow/2'>N-terminal domain</scene> of the protein. | + | Here is the <scene name='57/579708/N_zoom_rainbow/2'>N-terminal domain</scene> of the protein. MANF N-terminus is a saposin-like domain (SAPLIP). SAPLIPs, although they have a rather low sequence homology, have a high structural homology and seem to all share the ability to binf lipids [Reference]. However, since the biological receptor and interaction partners are either completely (receptor(s)) or largely (interactions with other proteins) unknown, the precise molecular mechanisms remain elusive. However, it has been proposed, that the neuroprotective ability of MANF may reside in it's N-terminal domain. |
===C-terminal domain=== | ===C-terminal domain=== | ||
| - | Here is the <scene name='57/579708/C_zoom_rainbow/2'>C-terminal domain</scene> of the protein. | + | Here is the <scene name='57/579708/C_zoom_rainbow/2'>C-terminal domain</scene> of the protein. It is worth mentioning that residues 138-158 are not visible in the crystal structure, probably due to being natively unstructured. This also includes a RTDL sequence, which is homologous to the KDEL sequence, an ER-retention sequence. This places MANF biologically into the endoplasmic reticulum and the CKGC disulphide bridge, present also in the same region of the protein, suggests a role in ER-stress response. The same type of CKGC disulphide bridge is namely present in the reductases and disulphide isomerases. Thus, it has been suggested, that ER-stress response function may reside in the C-terminus of the protein. |
==MANF in disease== | ==MANF in disease== | ||
Revision as of 11:38, 9 May 2014
| This Sandbox is Reserved from 01/04/2014, through 30/06/2014 for use in the course "510042. Protein structure, function and folding" taught by Prof Adrian Goldman, Tommi Kajander, Taru Meri, Konstantin Kogan and Juho Kellosalo at the University of Helsinki. This reservation includes Sandbox Reserved 923 through Sandbox Reserved 947. |
To get started:
More help: Help:Editing |
Introduction
Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) forms an evultionarily conserved distinct family of growth factors together with the Cerebral Dopamine Neurotrophic Factor (CDNF) [Reference]. MANF was first discovered as an arginine rich protein, which was mutated in early stage tumors, thus it's earlier name ARMET-1 (Arginine-Rich, Mutated in Early-stage Tumors). Since it's discovery, it has been widely studied and has proven useful in a number of experimental setups, among which protective functions in models of strok [Reference], 6-hydroxy dopamine [Reference]. It's receptor remains still to be discovered, however lately a rather intruiging finding was published, namely the interaction between MANF and glucose related protein 78 (GRP78), a protein of the unfolded protein response (UPR) [Reference]. This suggests another important role for MANF in the regulation of UPR, a ubiquitously occuring process in a living organism and evolutionarily heavily conserved.
In (year?) the crystal structure of MANF was solved by Parkash et al, giving important insight into the function of MANF. The further content of this page is directed to dissecting the structure/function relation of the MANF protein.
| |||||||||||
