8dzv

From Proteopedia

(Difference between revisions)

Current revision

Chicken anti-cardiac Troponin I antibody in complex with peptide

Structural highlights

8dzv is a 2 chain structure with sequence from Gallus gallus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.2Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

TNNI3_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.

Function

TNNI3_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

↑ Kimura A, Harada H, Park JE, Nishi H, Satoh M, Takahashi M, Hiroi S, Sasaoka T, Ohbuchi N, Nakamura T, Koyanagi T, Hwang TH, Choo JA, Chung KS, Hasegawa A, Nagai R, Okazaki O, Nakamura H, Matsuzaki M, Sakamoto T, Toshima H, Koga Y, Imaizumi T, Sasazuki T. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nat Genet. 1997 Aug;16(4):379-82. PMID:9241277 doi:10.1038/ng0897-379
↑ Niimura H, Patton KK, McKenna WJ, Soults J, Maron BJ, Seidman JG, Seidman CE. Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation. 2002 Jan 29;105(4):446-51. PMID:11815426
↑ Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation. 2003 May 6;107(17):2227-32. Epub 2003 Apr 21. PMID:12707239 doi:10.1161/01.CIR.0000066323.15244.54
↑ Erdmann J, Daehmlow S, Wischke S, Senyuva M, Werner U, Raible J, Tanis N, Dyachenko S, Hummel M, Hetzer R, Regitz-Zagrosek V. Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy. Clin Genet. 2003 Oct;64(4):339-49. PMID:12974739
↑ Ingles J, Doolan A, Chiu C, Seidman J, Seidman C, Semsarian C. Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling. J Med Genet. 2005 Oct;42(10):e59. PMID:16199542 doi:10.1136/jmg.2005.033886
↑ Mogensen J, Kubo T, Duque M, Uribe W, Shaw A, Murphy R, Gimeno JR, Elliott P, McKenna WJ. Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. J Clin Invest. 2003 Jan;111(2):209-16. PMID:12531876 doi:10.1172/JCI16336
↑ Murphy RT, Mogensen J, Shaw A, Kubo T, Hughes S, McKenna WJ. Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy. Lancet. 2004 Jan 31;363(9406):371-2. PMID:15070570 doi:10.1016/S0140-6736(04)15468-8
↑ 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. Design of Polarity-Dependent Immunosensors Based on the Structural Analysis of Engineered Antibodies. ACS Chem Biol. 2023 Jul 13. PMID:37440171 doi:10.1021/acschembio.3c00303

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8dzv"

Categories: Gallus gallus | Homo sapiens | Large Structures | Conroy PJ | Law HP

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8dzv is ON HOLD  until Paper Publication
+==Chicken anti-cardiac Troponin I antibody in complex with peptide==
+<StructureSection load='8dzv' size='340' side='right'caption='[[8dzv]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8dzv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DZV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DZV FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=8dzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dzv OCA], [https://pdbe.org/8dzv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dzv RCSB], [https://www.ebi.ac.uk/pdbsum/8dzv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dzv ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/TNNI3_HUMAN TNNI3_HUMAN] Defects in TNNI3 are the cause of familial hypertrophic cardiomyopathy type 7 (CMH7) [MIM:[https://omim.org/entry/613690 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.<ref>PMID:9241277</ref> <ref>PMID:11815426</ref> <ref>PMID:12707239</ref> <ref>PMID:12974739</ref> <ref>PMID:16199542</ref>   Defects in TNNI3 are the cause of familial restrictive cardiomyopathy type 1 (RCM1) [MIM:[https://omim.org/entry/115210 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.<ref>PMID:12531876</ref>   Defects in TNNI3 are the cause of cardiomyopathy dilated type 2A (CMD2A) [MIM:[https://omim.org/entry/611880 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.<ref>PMID:15070570</ref>   Defects in TNNI3 are the cause of cardiomyopathy dilated type 1FF (CMD1FF) [MIM:[https://omim.org/entry/613286 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.
+== Function ==
+[https://www.uniprot.org/uniprot/TNNI3_HUMAN TNNI3_HUMAN] Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
+<div style="background-color:#fffaf0;">
+== 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.
-Authors: Conroy, P.J., Law, H.P.
+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<ref>PMID:37440171</ref>
-Description: Chicken anti-cardiac Troponin I antibody in complex with peptide
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Conroy, P.J]]
+<div class="pdbe-citations 8dzv" style="background-color:#fffaf0;"></div>
-[[Category: Law, H.P]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Gallus gallus]]
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Conroy PJ]]
+[[Category: Law HP]]

8dzv

From Proteopedia

Current revision

Chicken anti-cardiac Troponin I antibody in complex with peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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