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| | ==Structure of the N-terminal BARpeptide in SDS micelles== | | ==Structure of the N-terminal BARpeptide in SDS micelles== |
| - | <StructureSection load='2rmy' size='340' side='right'caption='[[2rmy]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2rmy' size='340' side='right'caption='[[2rmy]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2rmy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RMY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RMY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2rmy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RMY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RMY FirstGlance]. <br> |
| - | </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=2rmy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rmy OCA], [https://pdbe.org/2rmy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rmy RCSB], [https://www.ebi.ac.uk/pdbsum/2rmy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rmy ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2rmy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rmy OCA], [https://pdbe.org/2rmy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rmy RCSB], [https://www.ebi.ac.uk/pdbsum/2rmy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rmy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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>
| + | [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 == |
| - | [[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.
| + | [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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Balbach, J]] | + | [[Category: Balbach J]] |
| - | [[Category: Loew, C]] | + | [[Category: Loew C]] |
| - | [[Category: Weininger, U]] | + | [[Category: Weininger U]] |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Anti-oncogene]]
| + | |
| - | [[Category: Barpeptide]]
| + | |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Coiled coil]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Developmental protein]]
| + | |
| - | [[Category: Differentiation]]
| + | |
| - | [[Category: Endocytosis]]
| + | |
| - | [[Category: Host-virus interaction]]
| + | |
| - | [[Category: Micelle]]
| + | |
| - | [[Category: Nmr-structure]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| 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
BAR domains (Bin/Amphiphysin/Rvs-homology) generate and sense membrane curvature by binding the negatively charged membrane to their positively charged concave surfaces. N-BAR domains contain an N-terminal extension (helix-0) predicted to form an amphipathic helix upon membrane binding. We determined the NMR structure and nano-to-picosecond dynamics of helix-0 of the human Bin1/Amphiphysin II BAR domain in SDS and DPC micelles. Molecular dynamic simulations of this 34 amino acid peptide revealed electrostatic and hydrophobic interactions with the detergent molecules, which induce helical structure formation from residues 8-10 towards the C-terminus. The orientation in the micelles was experimentally confirmed by backbone amide proton exchange. Both simulation and experiment indicate that the N-terminal region is disordered, and the peptide curves to adopt the micelle shape. Deletion of helix-0 reduces tubulation of liposomes by the BAR domain, whereas the helix-0 peptide itself was fusogenic. These findings support models for membrane curving by BAR domains, where helix-0 increases the binding affinity to the membrane and enhances curvature generation.
Structure and dynamics of Helix-0 of the N-BAR domain in Lipid Micelles and Bilayers.,Low C, Weininger U, Lee H, Schweimer K, Neundorf I, Beck-Sickinger AG, Pastor RW, Balbach J Biophys J. 2008 Jul 25. PMID:18658220[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
- ↑ Low C, Weininger U, Lee H, Schweimer K, Neundorf I, Beck-Sickinger AG, Pastor RW, Balbach J. Structure and dynamics of Helix-0 of the N-BAR domain in Lipid Micelles and Bilayers. Biophys J. 2008 Jul 25. PMID:18658220 doi:http://dx.doi.org/biophysj.108.134155
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