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| | ==Amphiphysin SH3 in complex with Chikungunya virus nsP3 peptide== | | ==Amphiphysin SH3 in complex with Chikungunya virus nsP3 peptide== |
| - | <StructureSection load='5i22' size='340' side='right'caption='[[5i22]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='5i22' size='340' side='right'caption='[[5i22]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5i22]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Chikv Chikv] and [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I22 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I22 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5i22]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chikungunya_virus Chikungunya virus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I22 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BIN1, AMPHL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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=5i22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i22 OCA], [https://pdbe.org/5i22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i22 RCSB], [https://www.ebi.ac.uk/pdbsum/5i22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i22 ProSAT]</span></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=5i22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i22 OCA], [http://pdbe.org/5i22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i22 RCSB], [http://www.ebi.ac.uk/pdbsum/5i22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i22 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/BIN1_HUMAN BIN1_HUMAN]] Defects in BIN1 are the cause of centronuclear myopathy type 2 (CNM2) [MIM:[http://omim.org/entry/255200 255200]]. A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.<ref>PMID:17676042</ref> | + | [https://www.uniprot.org/uniprot/BIN1_HUMAN BIN1_HUMAN] Defects in BIN1 are the cause of centronuclear myopathy type 2 (CNM2) [MIM:[https://omim.org/entry/255200 255200]. A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.<ref>PMID:17676042</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BIN1_HUMAN BIN1_HUMAN]] May be involved in regulation of synaptic vesicle endocytosis. May act as a tumor suppressor and inhibits malignant cell transformation. | + | [https://www.uniprot.org/uniprot/BIN1_HUMAN BIN1_HUMAN] May be involved in regulation of synaptic vesicle endocytosis. May act as a tumor suppressor and inhibits malignant cell transformation. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chikv]] | + | [[Category: Chikungunya virus]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Aitio, O]] | + | [[Category: Aitio O]] |
| - | [[Category: Hellman, M]] | + | [[Category: Hellman M]] |
| - | [[Category: Permi, P]] | + | [[Category: Permi P]] |
| - | [[Category: Saksela, K]] | + | [[Category: Saksela K]] |
| - | [[Category: Tossavainen, H]] | + | [[Category: Tossavainen H]] |
| - | [[Category: Function: protein binding chikungunya virus nsp3 peptide]]
| + | |
| - | [[Category: Function: viral replication]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Disease
BIN1_HUMAN Defects in BIN1 are the cause of centronuclear myopathy type 2 (CNM2) [MIM:255200. A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.[1]
Function
BIN1_HUMAN May be involved in regulation of synaptic vesicle endocytosis. May act as a tumor suppressor and inhibits malignant cell transformation.
Publication Abstract from PubMed
We show that a peptide from Chikungunya virus nsP3 protein spanning residues 1728-1744 binds the amphiphysin-2 (BIN1) Src homology-3 (SH3) domain with an unusually high affinity (Kd 24 nM). Our NMR solution complex structure together with ITC data on several related viral and cellular peptide ligands reveal that this exceptional affinity originates from interactions between multiple basic residues in the target peptide and the extensive negatively charged binding surface of amphiphysin-2 SH3. Remarkably, these arginines show no fixed conformation in the complex structure indicating that a transient or fluctuating polyelectrostatic interaction accounts for this affinity. Thus, via optimization of such dynamic electrostatic forces viral peptides have evolved a superior binding affinity for amphiphysin-2 SH3 compared to typical cellular ligands, such as dynamin, thereby enabling hijacking of amphiphysin-2 SH3 regulated host cell processes by these viruses. Moreover, our data show that the previously described consensus sequence PxRPxR for amphiphysin SH3 ligands is inaccurate, and instead define it as an extended Class II binding motif PxxPxRpxR, where additional positive charges between the two constant arginine residues can give rise to extraordinary high SH3 binding affinity.
Structural Basis of the High-Affinity Interaction Between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2.,Tossavainen H, Aitio O, Hellman M, Saksela K, Permi P J Biol Chem. 2016 Jun 6. pii: jbc.M116.732412. PMID:27268056[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nicot AS, Toussaint A, Tosch V, Kretz C, Wallgren-Pettersson C, Iwarsson E, Kingston H, Garnier JM, Biancalana V, Oldfors A, Mandel JL, Laporte J. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy. Nat Genet. 2007 Sep;39(9):1134-9. Epub 2007 Aug 5. PMID:17676042 doi:10.1038/ng2086
- ↑ Tossavainen H, Aitio O, Hellman M, Saksela K, Permi P. Structural Basis of the High-Affinity Interaction Between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2. J Biol Chem. 2016 Jun 6. pii: jbc.M116.732412. PMID:27268056 doi:http://dx.doi.org/10.1074/jbc.M116.732412
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