Sandbox Reserved 1110
From Proteopedia
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Residue Count: '''236''' | Residue Count: '''236''' | ||
| - | 5LSD is the recombinant mouse '''Nerve Growth Factor (NGF)''', that does not bind to '''any ligand'''. | + | 5LSD is the recombinant mouse '''Nerve Growth Factor (NGF)''', that does not bind to '''any ligand'''. Therefore it allows conclusions on the features of its binding loops. Through 5LSD, 3 questions can be targeted: (i) how is the NGF N-terminus structured in the absence of ligands? (ii) how flexible/rigid are the loops and how does their dynamics may reflect on the overall structural plasticity of mature NGF? (iii) how much do the loops contribute to antibody recognition?<ref>PMID: 28083536</ref> |
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== Structure == | == Structure == | ||
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In the absence of partners, the NGF N-terminus has a strong tendency to fold into a '''helix'''. This challenges the current view that this region is unstructured. Experiments have shown that this N-terminus plays an important role in many processes, and its absence triggers a loss of affinity with the receptor '''TrkA'''. The loops, especially II and V, and the C-terminus are relatively more flexible than the more rigid β-sheet regions (showing hetNOE values lower than the average of 0.7). However, the loop variations are relatively small compared to the flexibility of the N- and C-termini, which indicates that the loops are plastic but not flexible. <ref>PMID: 28083536</ref> | In the absence of partners, the NGF N-terminus has a strong tendency to fold into a '''helix'''. This challenges the current view that this region is unstructured. Experiments have shown that this N-terminus plays an important role in many processes, and its absence triggers a loss of affinity with the receptor '''TrkA'''. The loops, especially II and V, and the C-terminus are relatively more flexible than the more rigid β-sheet regions (showing hetNOE values lower than the average of 0.7). However, the loop variations are relatively small compared to the flexibility of the N- and C-termini, which indicates that the loops are plastic but not flexible. <ref>PMID: 28083536</ref> | ||
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| - | == Differences and importance of unbound feature == | ||
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| - | In the crystal structures of free and bound NGF, the conformation of loop II Shows high plasticity. An Overall Opening of the structure occurs for accomodation of small ligands. | ||
== The neurotrophin family == | == The neurotrophin family == | ||
| - | The neurotrophins gather the proteins involved in many mechanisms essential for the growth, maintenance and survival of neuronal populations, As NGF is the prototype of this family, each recombinant form of it targets a special population of neurons in the central as in the peripheral nervous system. Each member of this family plays a role on the activation of one of the three tropomyosin-related kinase ('''Trk''') [http://proteopedia.org/wiki/index.php/High_affinity_nerve_growth_factor_receptor] receptor ('''TrkA, TrkB, and TrkC''') and activates the '''p75''' neurotrophin receptor, a member of the tumor necrosis factor receptor superfamily. | + | The neurotrophins gather the proteins involved in many mechanisms essential for the growth, maintenance and survival of neuronal populations, As NGF is the prototype of this family, each recombinant form of it targets a special population of neurons in the central as well as in the peripheral nervous system. Each member of this family plays a role on the activation of one of the three tropomyosin-related kinase ('''Trk''') [http://proteopedia.org/wiki/index.php/High_affinity_nerve_growth_factor_receptor] receptor ('''TrkA, TrkB, and TrkC''') and activates the '''p75''' neurotrophin receptor, a member of the tumor necrosis factor receptor superfamily. |
The members of the neurotrophin family are then as useful in prenatal organisms for the development of cortexes and in adulthood, where they control synaptic function and plasticity and sustain neuronal cell survival. | The members of the neurotrophin family are then as useful in prenatal organisms for the development of cortexes and in adulthood, where they control synaptic function and plasticity and sustain neuronal cell survival. | ||
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As NGF is the prototype of the neurotrophin family, a better understanding of NGF could lead to a better understanding of the whole family. A better knowledge of NGF, i.e. through 5LSD, is supportive. | As NGF is the prototype of the neurotrophin family, a better understanding of NGF could lead to a better understanding of the whole family. A better knowledge of NGF, i.e. through 5LSD, is supportive. | ||
| - | It has been shown that Alzheimer’s Disease and the ratio of ProNGF/NGF ('''ProNGF''' being the pre-mutine form of NGF) are linked <ref>PMID: 23538417</ref> , and | + | It has been shown that Alzheimer’s Disease and the ratio of ProNGF/NGF ('''ProNGF''' being the pre-mutine form of NGF) are linked <ref>PMID: 23538417</ref> , and that this ratio plays a role in neurodegeneration. The matter would be to understand how the different forms of NGF interact, then being able to understand the interactions between the ligands and the loops by modifying the 5LSD structure could help in the medical way. Moreover, it has been experimentally and clinically shown that NGF plays a role in the '''pain states'''. Understanding and developing anti-NGF could advance the research of safe and efficient analgesics. <ref>PMID:24691709</ref> |
In fact, NGF fragments would also lead scientist to their anti-NGF as 5LSD permitted to detect the anti-NGF antagonist antibody '''αD11'''. | In fact, NGF fragments would also lead scientist to their anti-NGF as 5LSD permitted to detect the anti-NGF antagonist antibody '''αD11'''. | ||
Revision as of 10:28, 17 January 2020
| This Sandbox is Reserved from 25/11/2019, through 30/9/2020 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1091 through Sandbox Reserved 1115. |
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