8dzv
Chicken anti-cardiac Troponin I antibody in complex with peptide
Structural highlights
DiseaseTNNI3_HUMAN Defects in TNNI3 are the cause of familial hypertrophic cardiomyopathy type 7 (CMH7) [MIM:613690. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.[1] [2] [3] [4] [5] Defects in TNNI3 are the cause of familial restrictive cardiomyopathy type 1 (RCM1) [MIM:115210. RCM1 is a heart muscle disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function.[6] Defects in TNNI3 are the cause of cardiomyopathy dilated type 2A (CMD2A) [MIM:611880. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.[7] Defects in TNNI3 are the cause of cardiomyopathy dilated type 1FF (CMD1FF) [MIM:613286. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. FunctionTNNI3_HUMAN Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. Publication Abstract from PubMed"Reagentless" immunosensors are emerging to address the challenge of practical and sensitive detection of important biomarkers in real biological samples without the need for multistep assays and user intervention, with applications ranging from research tools to point-of-care diagnostics. Selective target binding to an affinity reagent is detected and reported in one step without the need for washing or additional reporters. In this study, we used a structure-guided approach to identify a mutation site in an antibody fragment for the polarity-dependent fluorophore, Anap, such that upon binding of the protein target cardiac troponin I, the Anap-labeled antibody would produce a detectable and dose-dependent shift in emission wavelength. We observed a significant emission wavelength shift of the Anap-labeled anti-cTnI mutant, with a blue shift of up to 37 nm, upon binding to the cTnI protein. Key differences in the resulting emission spectra between target peptides in comparison to whole proteins were also found; however, the affinity and binding characteristics remained unaffected when compared to the wild-type antibody. We also highlighted the potential flexibility of the approach by incorporating a near-infrared dye, IRDye800CW, into the same mutation site, which also resulted in a dose-dependent wavelength shift upon target incubation. These reagents can be used in experiments and devices to create simpler and more efficient biosensors across a range of research, medical laboratory, and point-of-care platforms. Design of Polarity-Dependent Immunosensors Based on the Structural Analysis of Engineered Antibodies.,Islam J, Conroy P, Fercher C, Kim M, Yaari Z, Jones M, Bell TDM, Caradoc-Davies T, Law R, Whisstock J, Heller D, Mahler S, Corrie S ACS Chem Biol. 2023 Aug 18;18(8):1863-1871. doi: 10.1021/acschembio.3c00303. Epub , 2023 Jul 13. PMID:37440171[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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