|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==X-ray crystal structural analysis of the complex between ALG-2 and Sec31A peptide== | | ==X-ray crystal structural analysis of the complex between ALG-2 and Sec31A peptide== |
| - | <StructureSection load='3wxa' size='340' side='right' caption='[[3wxa]], [[Resolution|resolution]] 2.36Å' scene=''> | + | <StructureSection load='3wxa' size='340' side='right'caption='[[3wxa]], [[Resolution|resolution]] 2.36Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3wxa]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WXA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3wxa]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WXA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.36Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDCD6, ALG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3wxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wxa OCA], [http://pdbe.org/3wxa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wxa RCSB], [http://www.ebi.ac.uk/pdbsum/3wxa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wxa ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3wxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wxa OCA], [https://pdbe.org/3wxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wxa RCSB], [https://www.ebi.ac.uk/pdbsum/3wxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wxa ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/SC31A_HUMAN SC31A_HUMAN]] A chromosomal aberration involving SEC31A is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;4)(p23;q21) with ALK. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PDCD6_HUMAN PDCD6_HUMAN]] Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. May mediate Ca(2+)-regulated signals along the death pathway (By similarity). Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity.<ref>PMID:16132846</ref> <ref>PMID:19520058</ref> [[http://www.uniprot.org/uniprot/SC31A_HUMAN SC31A_HUMAN]] Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules (By similarity). | + | [https://www.uniprot.org/uniprot/PDCD6_HUMAN PDCD6_HUMAN] Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. May mediate Ca(2+)-regulated signals along the death pathway (By similarity). Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity.<ref>PMID:16132846</ref> <ref>PMID:19520058</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 3wxa" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3wxa" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cell death protein 3D structures|Cell death protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Kawasaki, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Maki, M]] | + | [[Category: Kawasaki M]] |
| - | [[Category: Shibata, H]] | + | [[Category: Maki M]] |
| - | [[Category: Suzuki, H]] | + | [[Category: Shibata H]] |
| - | [[Category: Takahashi, T]] | + | [[Category: Suzuki H]] |
| - | [[Category: Wakatsuki, S]] | + | [[Category: Takahashi T]] |
| - | [[Category: Apoptosis]]
| + | [[Category: Wakatsuki S]] |
| - | [[Category: Apoptosis-transport protein complex]]
| + | |
| - | [[Category: Calcium binding]]
| + | |
| - | [[Category: Endoplasmic reticulum]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Penta-ef-hand protein]]
| + | |
| - | [[Category: Transport]]
| + | |
| Structural highlights
Function
PDCD6_HUMAN Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. May mediate Ca(2+)-regulated signals along the death pathway (By similarity). Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity.[1] [2]
Publication Abstract from PubMed
ALG-2, a 22-kDa penta-EF-hand protein, is involved in cell death, signal transduction, membrane trafficking, etc., by interacting with various proteins in mammalian cells in a Ca2+-dependent manner. Most known ALG-2-interacting proteins contain proline-rich regions in which either PPYPXnYP (type 1 motif) or PXPGF (type 2 motif) is commonly found. Previous X-ray crystal structural analysis of the complex between ALG-2 and an ALIX peptide revealed that the peptide binds to the two hydrophobic pockets. In the present study, we resolved the crystal structure of the complex between ALG-2 and a peptide of Sec31A (outer shell component of coat complex II, COPII; containing the type 2 motif) and found that the peptide binds to the third hydrophobic pocket (Pocket 3). While amino acid substitution of Phe85, a Pocket 3 residue, with Ala abrogated the interaction with Sec31A, it did not affect the interaction with ALIX. On the other hand, amino acid substitution of Tyr180, a Pocket 1 residue, with Ala caused loss of binding to ALIX, but maintained binding to Sec31A. We conclude that ALG-2 recognizes two types of motifs at different hydrophobic surfaces. Furthermore, based on the results of serial mutational analysis of the ALG-2-binding sites in Sec31A, the type 2 motif was newly defined.
Structural Analysis of the Complex between Penta-EF-Hand ALG-2 Protein and Sec31A Peptide Reveals a Novel Target Recognition Mechanism of ALG-2.,Takahashi T, Kojima K, Zhang W, Sasaki K, Ito M, Suzuki H, Kawasaki M, Wakatsuki S, Takahara T, Shibata H, Maki M Int J Mol Sci. 2015 Feb 6;16(2):3677-99. doi: 10.3390/ijms16023677. PMID:25667979[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lee JH, Rho SB, Chun T. Programmed cell death 6 (PDCD6) protein interacts with death-associated protein kinase 1 (DAPk1): additive effect on apoptosis via caspase-3 dependent pathway. Biotechnol Lett. 2005 Jul;27(14):1011-5. PMID:16132846 doi:http://dx.doi.org/10.1007/s10529-005-7869-x
- ↑ Okumura M, Ichioka F, Kobayashi R, Suzuki H, Yoshida H, Shibata H, Maki M. Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101. Biochem Biophys Res Commun. 2009 Aug 14;386(1):237-41. doi:, 10.1016/j.bbrc.2009.06.015. Epub 2009 Jun 9. PMID:19520058 doi:http://dx.doi.org/10.1016/j.bbrc.2009.06.015
- ↑ Takahashi T, Kojima K, Zhang W, Sasaki K, Ito M, Suzuki H, Kawasaki M, Wakatsuki S, Takahara T, Shibata H, Maki M. Structural Analysis of the Complex between Penta-EF-Hand ALG-2 Protein and Sec31A Peptide Reveals a Novel Target Recognition Mechanism of ALG-2. Int J Mol Sci. 2015 Feb 6;16(2):3677-99. doi: 10.3390/ijms16023677. PMID:25667979 doi:http://dx.doi.org/10.3390/ijms16023677
|
