title: Designing proteins to combat disease: Cardiac troponin C as an example.
abstract: Throughout history, muscle research has led to numerous scientific breakthroughs that have brought insight to a more general understanding of all biological processes. Potentially one of the most influential discoveries was the role of the second messenger calcium and its myriad of handling and sensing systems that mechanistically control muscle contraction. In this review we will briefly discuss the significance of calcium as a universal second messenger along with some of the most common calcium binding motifs in proteins, focusing on the EF-hand. We will also describe some of our approaches to rationally design calcium binding proteins to palliate, or potentially even cure cardiovascular disease. Considering not all failing hearts have the same etiology, genetic background and co-morbidities, personalized therapies will need to be developed. We predict designer proteins will open doors for unprecedented personalized, and potentially, even generalized medicines as gene therapy or protein delivery techniques come to fruition.
authors.affiliation: Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA. Electronic address: davis.812@osu.edu.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Davis
authors.affiliation: Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Shettigar
authors.affiliation: Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Svetlana B
authors.initials: SB
authors.lastname: Tikunova
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT, USA.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Little
authors.affiliation: Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Jalal K
authors.initials: JK
authors.lastname: Siddiqui
authors.affiliation: Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Paul M L
authors.initials: PM
authors.lastname: Janssen
authors.affiliation: Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Ziolo
authors.affiliation: Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Shane D
authors.initials: SD
authors.lastname: Walton
mesh_terms: D000818:Animals; D017302:Annexins / Q000737:chemistry; D001665:Binding Sites; D002021:Buffers; D002118:Calcium / Q000737:chemistry; D002135:Calcium-Binding Proteins / Q000737:chemistry; D002147:Calmodulin / Q000737:chemistry; D002309:Cardiology; D020832:EF Hand Motifs; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009119:Muscle Contraction; D009206:Myocardium / Q000378:metabolism*; D010320:Parvalbumins / Q000737:chemistry; D015202:Protein Engineering; D015290:Second Messenger Systems; D019209:Troponin C / Q000737:chemistry*
chemical_list: D017302:Annexins; D002021:Buffers; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D010320:Parvalbumins; D019209:Troponin C; D002118:Calcium
keywords: Cardiac; EF-hand; Gene therapy; Protein engineering; Therapeutic; Troponin