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6kn8
From Proteopedia
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==Structure of human cardiac thin filament in the calcium bound state== | ==Structure of human cardiac thin filament in the calcium bound state== | ||
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6kn8]] is a 29 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KN8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KN8 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6kn8]] is a 29 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KN8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KN8 FirstGlance]. <br> | ||
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<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
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[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
Revision as of 22:26, 6 March 2020
Structure of human cardiac thin filament in the calcium bound state
Structural highlights
Disease[TNNC1_HUMAN] Defects in TNNC1 are the cause of cardiomyopathy dilated type 1Z (CMD1Z) [MIM:611879]. 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.[1] Defects in TNNC1 are the cause of familial hypertrophic cardiomyopathy type 13 (CMH13) [MIM:613243]. 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.[2] [3] [4] [5] [TNNT2_HUMAN] Defects in TNNT2 are the cause of familial hypertrophic cardiomyopathy type 2 (CMH2) [MIM:115195]. 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.[6] [7] [8] [9] [10] [:][11] [12] [13] [14] [15] [16] [17] [18] Defects in TNNT2 are the cause of cardiomyopathy dilated type 1D (CMD1D) [MIM:601494]. 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.[19] [20] [21] [22] [23] Defects in TNNT2 are the cause of familial restrictive cardiomyopathy type 3 (RCM3) [MIM:612422]. Restrictive cardiomyopathy is a heart 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.[24] [TPM1_HUMAN] Left ventricular noncompaction;Familial isolated hypertrophic cardiomyopathy;Familial isolated dilated cardiomyopathy. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. [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.[25] [26] [27] [28] [29] 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.[30] 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.[31] 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[TNNC1_HUMAN] Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments. [TNNT2_HUMAN] Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. [ACTS_RABIT] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [TPM1_HUMAN] Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments. [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 PubMedContraction of striated muscles is driven by cyclic interactions of myosin head projecting from the thick filament with actin filament and is regulated by Ca(2+) released from sarcoplasmic reticulum. Muscle thin filament consists of actin, tropomyosin and troponin, and Ca(2+) binding to troponin triggers conformational changes of troponin and tropomyosin to allow actin-myosin interactions. However, the structural changes involved in this regulatory mechanism remain unknown. Here we report the structures of human cardiac muscle thin filament in the absence and presence of Ca(2+) by electron cryomicroscopy. Molecular models in the two states built based on available crystal structures reveal the structures of a C-terminal region of troponin I and an N-terminal region of troponin T in complex with the head-to-tail junction of tropomyosin together with the troponin core on actin filament. Structural changes of the thin filament upon Ca(2+) binding now reveal the mechanism of Ca(2+) regulation of muscle contraction. Cardiac muscle thin filament structures reveal calcium regulatory mechanism.,Yamada Y, Namba K, Fujii T Nat Commun. 2020 Jan 9;11(1):153. doi: 10.1038/s41467-019-14008-1. PMID:31919429[32] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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