1py1
From Proteopedia
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| - | [[Image:1py1.gif|left|200px]] | + | [[Image:1py1.gif|left|200px]] |
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| - | '''Complex of GGA1-VHS domain and beta-secretase C-terminal phosphopeptide''' | + | {{Structure |
| + | |PDB= 1py1 |SIZE=350|CAPTION= <scene name='initialview01'>1py1</scene>, resolution 2.60Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= GGA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Complex of GGA1-VHS domain and beta-secretase C-terminal phosphopeptide''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1PY1 is a [ | + | 1PY1 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PY1 OCA]. |
==Reference== | ==Reference== | ||
| - | Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins., He X, Zhu G, Koelsch G, Rodgers KK, Zhang XC, Tang J, Biochemistry. 2003 Oct 28;42(42):12174-80. PMID:[http:// | + | Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins., He X, Zhu G, Koelsch G, Rodgers KK, Zhang XC, Tang J, Biochemistry. 2003 Oct 28;42(42):12174-80. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14567678 14567678] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: vhs domain of gga1]] | [[Category: vhs domain of gga1]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:30:27 2008'' |
Revision as of 11:30, 20 March 2008
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| , resolution 2.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | GGA1 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Complex of GGA1-VHS domain and beta-secretase C-terminal phosphopeptide
Overview
Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease that initiates the hydrolysis of beta-amyloid precursor protein (APP) leading to the production of amyloid-beta and the onset of Alzheimer's disease (AD). Both memapsin 2 and APP are transported from the cell surface to endosomes where APP hydrolysis takes place. Thus, the intracellular transport mechanism of memapsin 2 is important for understanding the pathogenesis of AD. We have previously shown that the cytosolic domain of memapsin 2 contains an acid-cluster-dileucine (ACDL) motif that binds the VHS domain of GGA proteins (He et al. (2002) FEBS Lett. 524, 183-187). This mechanism is the presumed recognition step for the vesicular packaging of memapsin 2 for its transport to endosomes. The phosphorylation of a serine residue within the ACDL motif has been reported to regulate the recycling of memapsin 2 from early endosomes back to the cell surface. Here, we report a study on the memapsin 2/VHS domain interaction. Using isothermal titration calorimetry, the dissociation constant, K(d), values are 4.0 x 10(-4), 4.1 x 10(-4), and 3.1 x 10(-4) M for VHS domains from GGA1, GGA2, and GGA3, respectively. With the serine residue replaced by phosphoserine, the K(d) decreased about 10-, 4-, and 14-fold for the same three VHS domains. A crystal structure of the complex between memapsin 2 phosphoserine peptide and GGA1 VHS was solved at 2.6 A resolution. The side chain of the phosphoserine group does not interact with the VHS domain but forms an ionic interaction with the side chain of the C-terminal lysine of the ligand peptide. Energy calculation of the binding of native and phosphorylated peptides to VHS domains suggests that this intrapeptide ionic bond in solution may reduce the change in binding entropy and thus increase binding affinity.
About this Structure
1PY1 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins., He X, Zhu G, Koelsch G, Rodgers KK, Zhang XC, Tang J, Biochemistry. 2003 Oct 28;42(42):12174-80. PMID:14567678
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