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From Proteopedia
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{{Sandbox_ESBS_2019}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | {{Sandbox_ESBS_2019}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | ||
| - | + | ==5LSD Structure== | |
| + | <StructureSection load='5LSD' size='350' side='right' caption='Mouse recombinant Nerve Growth Factor (PDB entry [[5LSD]])' scene=''> | ||
== 5LSD== | == 5LSD== | ||
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It is 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> | It is 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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| - | == The neurotrophin family == | ||
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| - | 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 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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== Structure == | == Structure == | ||
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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. | 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. | ||
| + | </StructureSection> | ||
| + | |||
| + | == 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 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. | ||
== Disease and use in Biotechnologies/ Relevance == | == Disease and use in Biotechnologies/ Relevance == | ||
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Contents |
5LSD Structure
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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) [1] 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.
Disease and use in Biotechnologies/ Relevance
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, and therefor that this ratio plays a role in neurodegeneration, 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 proved that NGF play a role in the pain states, then understanding and developing anti-NGF could help in the search of safe and efficient analgesics. [3] In fact, NGF fragments would also lead scientist to their anti-NGF as 5LSD permitted to detect the anti-NGF antagonist antibody αD11.
The NMR structure of 5LSD lead to the conclusion that NGF has long plastic but relatively rigid loops, which is of crucial importance for future drug design.[4]
This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
References
- ↑ Paoletti F, de Chiara C, Kelly G, Covaceuszach S, Malerba F, Yan R, Lamba D, Cattaneo A, Pastore A. Conformational Rigidity within Plasticity Promotes Differential Target Recognition of Nerve Growth Factor. Front Mol Biosci. 2016 Dec 26;3:83. doi: 10.3389/fmolb.2016.00083. eCollection, 2016. PMID:28083536 doi:http://dx.doi.org/10.3389/fmolb.2016.00083
- ↑ Paoletti F, de Chiara C, Kelly G, Covaceuszach S, Malerba F, Yan R, Lamba D, Cattaneo A, Pastore A. Conformational Rigidity within Plasticity Promotes Differential Target Recognition of Nerve Growth Factor. Front Mol Biosci. 2016 Dec 26;3:83. doi: 10.3389/fmolb.2016.00083. eCollection, 2016. PMID:28083536 doi:http://dx.doi.org/10.3389/fmolb.2016.00083
- ↑ Bannwarth B, Kostine M. Targeting nerve growth factor (NGF) for pain management: what does the future hold for NGF antagonists? Drugs. 2014 Apr;74(6):619-26. doi: 10.1007/s40265-014-0208-6. PMID:24691709 doi:http://dx.doi.org/10.1007/s40265-014-0208-6
- ↑ Bannwarth B, Kostine M. Targeting nerve growth factor (NGF) for pain management: what does the future hold for NGF antagonists? Drugs. 2014 Apr;74(6):619-26. doi: 10.1007/s40265-014-0208-6. PMID:24691709 doi:http://dx.doi.org/10.1007/s40265-014-0208-6
