Sandbox Reserved 938
From Proteopedia
(Difference between revisions)
| Line 5: | Line 5: | ||
==Introduction== | ==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 | + | 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 stroke [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 | + | In (year?) the crystal structure of MANF was solved by Parkash et al, giving important insights into the function of MANF. The further content of this page is directed to dissecting the structure/function relation of the MANF protein. |
<StructureSection load='2W51' size='350' side='right' caption='MANF' scene='57/579708/Manf_rainbow/2'> | <StructureSection load='2W51' size='350' side='right' caption='MANF' scene='57/579708/Manf_rainbow/2'> | ||
| Line 21: | Line 21: | ||
===C-terminal domain=== | ===C-terminal domain=== | ||
| - | 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 | + | 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. The RTDL sequence is also required for the secretion in response to ER-stress [Reference]. |
==MANF in disease== | ==MANF in disease== | ||
Revision as of 11:45, 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 stroke [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 insights into the function of MANF. The further content of this page is directed to dissecting the structure/function relation of the MANF protein.
| |||||||||||
