Tau protein: Difference between revisions
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<StructureSection load='2MZ7' size='350' side='right' scene='' caption='Human tau protein (PBD codes: [[2mz7]], [[4np8]])'> | |||
==Structure and Function == | ==Structure and Function == | ||
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The human '''tau protein''', encoded by chromosome 17q21, has a natively unfolded protein structure, which contributes to its flexibility and ability to stabilize functional microtubules <ref name="mandelkow">PMID: 22762014</ref>. Specifically, its primary structure, consisting of <scene name='71/716561/Primary_tau/1'>serines, threonines, aspartates, glutamates, lysines, arginines, prolines, and aromatics</scene>, is highly hydrophilic compared to other cytosolic proteins <ref name="mandelkow"/>. It has a predominantly acidic N-terminal region, a proline-rich middle region, and a relatively neutral C-terminal region <ref name="mandelkow"/>. | The human '''tau protein''', encoded by chromosome 17q21, has a natively unfolded protein structure, which contributes to its flexibility and ability to stabilize functional microtubules <ref name="mandelkow">PMID: 22762014</ref>. Specifically, its primary structure, consisting of <scene name='71/716561/Primary_tau/1'>serines, threonines, aspartates, glutamates, lysines, arginines, prolines, and aromatics</scene>, is highly hydrophilic compared to other cytosolic proteins <ref name="mandelkow"/>. It has a predominantly acidic N-terminal region, a proline-rich middle region, and a relatively neutral C-terminal region <ref name="mandelkow"/>. | ||
Additionally, tau has a transient secondary structure of α-helices, β-pleated sheets, and a poly-proline II helix <ref name="mandelkow"/>. Tau does not resemble a globular protein, but has characteristics of a denatured, unfolded protein which contributes to its overall hydrophilicity <ref name="schweers">PMID: 7929085</ref>. It can also interact with other tau proteins to form <scene name='71/716561/Tau_aggregation/1'>aggregations</scene>. | Additionally, tau has a transient secondary structure of α-helices, β-pleated sheets, and a poly-proline II helix <ref name="mandelkow"/>. Tau does not resemble a globular protein, but has characteristics of a denatured, unfolded protein which contributes to its overall hydrophilicity <ref name="schweers">PMID: 7929085</ref>. It can also interact with other tau proteins to form <scene name='71/716561/Tau_aggregation/1'>aggregations</scene>. | ||
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The phosphorylation state of tau directly affects proper assembly and stabilization of microtubules <ref name="Kolarova">PMID: 22690349</ref>. Phosphorylation is greatly increased when mutations of the tau protein are present <ref name="Alonso">PMID: 15190058</ref>. Phosphate groups on a highly phosphorylated tau may disrupt non-covalent interactions between the protein and microtubules, which may reduce tubulin stability and impair axonal transport. Thus, any abnormalities in the protein’s phosphorylation state may contribute to neurodegeneration, as described below <ref name="Rodriguez">PMID: 15272267</ref>. | The phosphorylation state of tau directly affects proper assembly and stabilization of microtubules <ref name="Kolarova">PMID: 22690349</ref>. Phosphorylation is greatly increased when mutations of the tau protein are present <ref name="Alonso">PMID: 15190058</ref>. Phosphate groups on a highly phosphorylated tau may disrupt non-covalent interactions between the protein and microtubules, which may reduce tubulin stability and impair axonal transport. Thus, any abnormalities in the protein’s phosphorylation state may contribute to neurodegeneration, as described below <ref name="Rodriguez">PMID: 15272267</ref>. | ||
[[Image:PhosphorylatedTau.png| | [[Image:PhosphorylatedTau.png|500px|thumb|Role of human tau in stabilization of microtubules through tubulin binding domains (blue). Phosphorylation (pink) of tau can directly regulate its interaction with microtubules and its role in axonal transport <ref name="Kolarova"/>]] | ||
==Disease Relation== | ==Disease Relation== | ||
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'''Parkinson’s Disease''' | '''Parkinson’s Disease''' | ||
Protein aggregation also exists in patients suffering from Parkinson’s disease, specifically within the substantia nigra of the midbrain <ref name="Ross">PMID: 15272267</ref>. Immunohistochemical studies reveal that abnormally phosphorylated tau proteins are partially involved in the development of Lewy bodies, protein aggregates, within the substantia nigra <ref name="Ishizawa">PMID: 12722831</ref>. Lewy bodies may be involved in the neurodegeneration of dopaminergic neurons within this area <ref name="Ross"/>. | Protein aggregation also exists in patients suffering from Parkinson’s disease, specifically within the substantia nigra of the midbrain <ref name="Ross">PMID: 15272267</ref>. Immunohistochemical studies reveal that abnormally phosphorylated tau proteins are partially involved in the development of Lewy bodies, protein aggregates, within the substantia nigra <ref name="Ishizawa">PMID: 12722831</ref>. Lewy bodies may be involved in the neurodegeneration of dopaminergic neurons within this area <ref name="Ross"/>. | ||
==3D Structures of tau protein== | |||
==3D Structures of protein | [[Tau protein 3D structures]] | ||
</StructureSection> | |||
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==References== | ==References== | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | |||