1rw6: Difference between revisions
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|GENE= APP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= APP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rw6 OCA], [http://www.ebi.ac.uk/pdbsum/1rw6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1rw6 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Amyloid beta-peptide, which forms neuronal and vascular amyloid deposits in Alzheimer's disease, is derived from an integral membrane protein precursor. The biological function of the precursor is currently unclear. Here we describe the X-ray structure of E2, the largest of the three conserved domains of the precursor. The structure of E2 consists of two coiled-coil substructures connected through a continuous helix and bears an unexpected resemblance to the spectrin family of protein structures. E2 can reversibly dimerize in the solution, and the dimerization occurs along the longest dimension of the molecule in an antiparallel orientation, which enables the N-terminal substructure of one monomer to pack against the C-terminal substructure of a second monomer. Heparan sulfate proteoglycans, the putative ligand for the precursor present in extracellular matrix, bind to E2 at a conserved and positively charged site near the dimer interface. | Amyloid beta-peptide, which forms neuronal and vascular amyloid deposits in Alzheimer's disease, is derived from an integral membrane protein precursor. The biological function of the precursor is currently unclear. Here we describe the X-ray structure of E2, the largest of the three conserved domains of the precursor. The structure of E2 consists of two coiled-coil substructures connected through a continuous helix and bears an unexpected resemblance to the spectrin family of protein structures. E2 can reversibly dimerize in the solution, and the dimerization occurs along the longest dimension of the molecule in an antiparallel orientation, which enables the N-terminal substructure of one monomer to pack against the C-terminal substructure of a second monomer. Heparan sulfate proteoglycans, the putative ligand for the precursor present in extracellular matrix, bind to E2 at a conserved and positively charged site near the dimer interface. | ||
==Disease== | |||
Known disease associated with this structure: Alzheimer disease-1, APP-related OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=104760 104760]], Amyloidosis, cerebroarterial, Dutch type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=104760 104760]], Amyloidosis, cerebroarterial, Iowa type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=104760 104760]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: dimer]] | [[Category: dimer]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:33:50 2008'' | ||
Revision as of 20:33, 30 March 2008
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| 1rw6, resolution 2.8Å | |||||||||||||
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| Gene: | APP (Homo sapiens) | ||||||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
human APP core domain
Overview
Amyloid beta-peptide, which forms neuronal and vascular amyloid deposits in Alzheimer's disease, is derived from an integral membrane protein precursor. The biological function of the precursor is currently unclear. Here we describe the X-ray structure of E2, the largest of the three conserved domains of the precursor. The structure of E2 consists of two coiled-coil substructures connected through a continuous helix and bears an unexpected resemblance to the spectrin family of protein structures. E2 can reversibly dimerize in the solution, and the dimerization occurs along the longest dimension of the molecule in an antiparallel orientation, which enables the N-terminal substructure of one monomer to pack against the C-terminal substructure of a second monomer. Heparan sulfate proteoglycans, the putative ligand for the precursor present in extracellular matrix, bind to E2 at a conserved and positively charged site near the dimer interface.
Disease
Known disease associated with this structure: Alzheimer disease-1, APP-related OMIM:[104760], Amyloidosis, cerebroarterial, Dutch type OMIM:[104760], Amyloidosis, cerebroarterial, Iowa type OMIM:[104760]
About this Structure
1RW6 is a Single protein structure of sequence from Homo sapiens. The following page contains interesting information on the relation of 1RW6 with [Amyloid-beta Precursor Protein]. Full crystallographic information is available from OCA.
Reference
The X-ray structure of an antiparallel dimer of the human amyloid precursor protein E2 domain., Wang Y, Ha Y, Mol Cell. 2004 Aug 13;15(3):343-53. PMID:15304215
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