2mg4: Difference between revisions
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==Computational design and experimental verification of a symmetric protein homodimer== | |||
<StructureSection load='2mg4' size='340' side='right'caption='[[2mg4]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2mg4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MG4 FirstGlance]. <br> | |||
</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=2mg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mg4 OCA], [https://pdbe.org/2mg4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mg4 RCSB], [https://www.ebi.ac.uk/pdbsum/2mg4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mg4 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Homodimers are the most common type of protein assembly in nature and have distinct features compared with heterodimers and higher order oligomers. Understanding homodimer interactions at the atomic level is critical both for elucidating their biological mechanisms of action and for accurate modeling of complexes of unknown structure. Computation-based design of novel protein-protein interfaces can serve as a bottom-up method to further our understanding of protein interactions. Previous studies have demonstrated that the de novo design of homodimers can be achieved to atomic-level accuracy by beta-strand assembly or through metal-mediated interactions. Here, we report the design and experimental characterization of a alpha-helix-mediated homodimer with C2 symmetry based on a monomeric Drosophila engrailed homeodomain scaffold. A solution NMR structure shows that the homodimer exhibits parallel helical packing similar to the design model. Because the mutations leading to dimer formation resulted in poor thermostability of the system, design success was facilitated by the introduction of independent thermostabilizing mutations into the scaffold. This two-step design approach, function and stabilization, is likely to be generally applicable, especially if the desired scaffold is of low thermostability. | |||
Computational design and experimental verification of a symmetric protein homodimer.,Mou Y, Huang PS, Hsu FC, Huang SJ, Mayo SL Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):10714-9. doi:, 10.1073/pnas.1505072112. Epub 2015 Aug 12. PMID:26269568<ref>PMID:26269568</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 2mg4" style="background-color:#fffaf0;"></div> | ||
[[Category: Hsu | == References == | ||
[[Category: Huang | <references/> | ||
[[Category: Huang | __TOC__ | ||
[[Category: Mou | </StructureSection> | ||
[[Category: Drosophila melanogaster]] | |||
[[Category: Large Structures]] | |||
[[Category: Hsu FC]] | |||
[[Category: Huang PS]] | |||
[[Category: Huang SJ]] | |||
[[Category: Mayo SL]] | |||
[[Category: Mou Y]] | |||
Latest revision as of 09:05, 15 May 2024
Computational design and experimental verification of a symmetric protein homodimerComputational design and experimental verification of a symmetric protein homodimer
Structural highlights
Publication Abstract from PubMedHomodimers are the most common type of protein assembly in nature and have distinct features compared with heterodimers and higher order oligomers. Understanding homodimer interactions at the atomic level is critical both for elucidating their biological mechanisms of action and for accurate modeling of complexes of unknown structure. Computation-based design of novel protein-protein interfaces can serve as a bottom-up method to further our understanding of protein interactions. Previous studies have demonstrated that the de novo design of homodimers can be achieved to atomic-level accuracy by beta-strand assembly or through metal-mediated interactions. Here, we report the design and experimental characterization of a alpha-helix-mediated homodimer with C2 symmetry based on a monomeric Drosophila engrailed homeodomain scaffold. A solution NMR structure shows that the homodimer exhibits parallel helical packing similar to the design model. Because the mutations leading to dimer formation resulted in poor thermostability of the system, design success was facilitated by the introduction of independent thermostabilizing mutations into the scaffold. This two-step design approach, function and stabilization, is likely to be generally applicable, especially if the desired scaffold is of low thermostability. Computational design and experimental verification of a symmetric protein homodimer.,Mou Y, Huang PS, Hsu FC, Huang SJ, Mayo SL Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):10714-9. doi:, 10.1073/pnas.1505072112. Epub 2015 Aug 12. PMID:26269568[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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