Human APP Intracellular Domain Complex with Fe65-PTB2: Difference between revisions

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'''Intracellular domain of human APP in complex with Fe65-PTB2'''
{{STRUCTURE_3dxc |  PDB=3dxc | SIZE=400| SCENE= |right|  CAPTION=Human amyloid precursor protein residues 739-770 complex with Fe65-PTB2, [[3dxc]]    }}Cleavage of the '''amyloid precursor protein''' (APP) is a crucial event in Alzheimer disease pathogenesis that creates the amyloid-beta peptide (Abeta) and liberates the carboxy-terminal APP intracellular domain (AICD) into the cytosol. <ref>PMID:18833287</ref> The study of interaction of the AICD and Fe65 protein is rather important, as Fe65 protein seems to be implicated in production of Abeta and in signalling in APP.
 
Cleavage of the amyloid precursor protein (APP) is a crucial event in Alzheimer disease pathogenesis that creates the amyloid-beta peptide (Abeta) and liberates the carboxy-terminal APP intracellular domain (AICD) into the cytosol. <ref>PMID:18833287</ref> The study of interaction of the AICD and Fe65 protein is rather important, as Fe65 protein seems to be implicated in production of Abeta and in signalling in APP.
{{STRUCTURE_3dxc |  PDB=3dxc  |  SCENE=  }}


== Structure ==
== Structure ==
This crystal structure contains 4 chains. <scene name='SANDBOX138/Chainesaandc/1'>A chain is identical to C chain</scene>. Each contains 140 residues: 4 helices and 7 strands. It's a part of the protein Fe65 binded with APP intracellular domain.
This crystal structure contains 4 chains. <scene name='SANDBOX138/Chainesaandc/1'>A chain is identical to C chain</scene>. Each contains 140 residues: 4 helices and 7 strands. It's a part of the protein Fe65 binded with APP intracellular domain.
<scene name='SANDBOX138/Chains_bandd/2'>Chains B and D are also identical</scene>. Each contains 35 residues: 2 helices and 1 strand. They represent APP intracellular domain.
<scene name='SANDBOX138/Chains_bandd/2'>Chains B and D are also identical</scene>. Each contains 35 residues: 2 helices and 1 strand. They represent APP intracellular domain.
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Fe65 is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression. Multiple alternatively spliced transcript variants have been described for this gene but some of their full length sequence is not known.<ref>[http://www.ncbi.nlm.nih.gov/protein/NP_001155.1?ordinalpos=1&itool=EntrezSystem2.PEntrez.Sequence.Sequence_ResultsPanel.Sequence_RVDocSum NCBI Reference Sequence: NP_001155.1]</ref>
Fe65 is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression. Multiple alternatively spliced transcript variants have been described for this gene but some of their full length sequence is not known.<ref>[http://www.ncbi.nlm.nih.gov/protein/NP_001155.1?ordinalpos=1&itool=EntrezSystem2.PEntrez.Sequence.Sequence_ResultsPanel.Sequence_RVDocSum NCBI Reference Sequence: NP_001155.1]</ref>


Fe65 plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as MAPK8/JNK1.Required for histone H4 acetylation at double-strand breaks (DSBs).Its ability to specifically bind modified histones and chromatin modifying enzymes such as KAT5/TIP60, probably explains its trancription activation activity. <ref>[http://www.uniprot.org/uniprot/O00213 UniProtKB/Swiss-Prot O00213 (APBB1_HUMAN)]</ref>
Fe65 plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as MAPK8/JNK1.Required for histone H4 acetylation at double-strand breaks (DSBs).Its ability to specifically bind modified histones and chromatin modifying enzymes such as KAT5/TIP60, probably explains its transcription activation activity. <ref>[http://www.uniprot.org/uniprot/O00213 UniProtKB/Swiss-Prot O00213 (APBB1_HUMAN)]</ref>


== Location ==
== Location ==
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Besides neuritic plaques neurofibrillary tangles containing hyperphosphorylated tau protein are characteristic in the neuropathology of Alzheimer’s disease. Hyperphosphorylated tau protein and accumulated Aβ protein are considered to coexist. <ref>PMID: 19158417</ref>
Besides neuritic plaques neurofibrillary tangles containing hyperphosphorylated tau protein are characteristic in the neuropathology of Alzheimer’s disease. Hyperphosphorylated tau protein and accumulated Aβ protein are considered to coexist. <ref>PMID: 19158417</ref>
==3D structures of amyloid precursor protein==
[[Amyloid precursor protein]]
===Additional Resources===
For additional information, see: [[Alzheimer's Disease]]
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== References ==
== References ==
Retrieved from "https://proteopedia.org/Human_APP_Intracellular_Domain_Complex_with_Fe65-PTB2"