6k67
Application of anti-helix antibodies in protein structure determination (9011-3LRH)
Structural highlights
DiseaseCALM3_HUMAN Catecholaminergic polymorphic ventricular tachycardia;Romano-Ward syndrome. The disease may be caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. FunctionCALM3_HUMAN Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding (PubMed:16760425, PubMed:31454269). Calcium-binding is required for the activation of calmodulin (PubMed:35568036, PubMed:16760425, PubMed:31454269). Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases (PubMed:16760425, PubMed:35568036). Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425).[1] [2] [3] (Microbial infection) Required for C.violaceum CopC arginine ADP-riboxanase activity.[4] [5] Publication Abstract from PubMedAntibodies are indispensable tools in protein engineering and structural biology. Antibodies suitable for structural studies should recognize the 3-dimensional (3D) conformations of target proteins. Generating such antibodies and characterizing their complexes with antigens take a significant amount of time and effort. Here, we show that we can expand the application of well-characterized antibodies by "transplanting" the epitopes that they recognize to proteins with completely different structures and sequences. Previously, several antibodies have been shown to recognize the alpha-helical conformation of antigenic peptides. We demonstrate that these antibodies can be made to bind to a variety of unrelated "off-target" proteins by modifying amino acids in the preexisting alpha helices of such proteins. Using X-ray crystallography, we determined the structures of the engineered protein-antibody complexes. All of the antibodies bound to the epitope-transplanted proteins, forming accurately predictable structures. Furthermore, we showed that binding of these antihelix antibodies to the engineered target proteins can modulate their catalytic activities by trapping them in selected functional states. Our method is simple and efficient, and it will have applications in protein X-ray crystallography, electron microscopy, and nanotechnology. Application of antihelix antibodies in protein structure determination.,Kim JW, Kim S, Lee H, Cho G, Kim SC, Lee H, Jin MS, Lee JO Proc Natl Acad Sci U S A. 2019 Aug 1. pii: 1910080116. doi:, 10.1073/pnas.1910080116. PMID:31371498[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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