Impact of calmodulin missense variants associated with congenital arrhythmia on the thermal stability and the degree of unfolding.

IF 3.8 2区生物学 Q2 GENETICS & HEREDITY

Human Genetics Pub Date : 2025-03-01 Epub Date: 2023-12-28 DOI:10.1007/s00439-023-02629-y

Giuditta Dal Cortivo, Valerio Marino, Davide Zamboni, Daniele Dell'Orco

引用次数: 0

Abstract

Thermal denaturation profiles of proteins that bind several ligands may deviate from the single transition, making their thermodynamic description challenging. We report an empirical method that estimates melting temperatures (T_m) from multi-transition thermal denaturation profiles of 16 variants of calmodulin (CaM) associated with congenital arrhythmia. Differences in T_m estimated by empirical fitting correlate (for apo CaM variants) with those obtained by thermodynamic models. Most CaM variants were more stable than the wild type (WT) in the absence of Ca²⁺, but less stable in the presence of Ca²⁺, and displayed either WT-like or higher unfolding percentages in their apo-form, as evaluated by circular dichroism spectroscopy.

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与先天性心律失常有关的钙调素错义变体对热稳定性和展开程度的影响

与多种配体结合的蛋白质的热变性曲线可能会偏离单一转变，因此对其进行热力学描述具有挑战性。我们报告了一种从与先天性心律失常有关的 16 种钙调素（CaM）变体的多转变热变性曲线估算熔化温度（Tm）的经验方法。经验拟合估算出的 Tm 差异（对于 apo CaM 变体）与热力学模型得出的 Tm 差异相关。大多数 CaM 变体在没有 Ca2+ 的情况下比野生型（WT）更稳定，但在有 Ca2+ 的情况下则不太稳定，而且根据圆二色光谱法的评估，它们的apo-form 要么显示出与 WT 相似的解折百分比，要么显示出更高的解折百分比。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Genetics 生物-遗传学

CiteScore

10.80

自引率

3.80%

发文量

审稿时长

1 months

期刊介绍： Human Genetics is a monthly journal publishing original and timely articles on all aspects of human genetics. The Journal particularly welcomes articles in the areas of Behavioral genetics, Bioinformatics, Cancer genetics and genomics, Cytogenetics, Developmental genetics, Disease association studies, Dysmorphology, ELSI (ethical, legal and social issues), Evolutionary genetics, Gene expression, Gene structure and organization, Genetics of complex diseases and epistatic interactions, Genetic epidemiology, Genome biology, Genome structure and organization, Genotype-phenotype relationships, Human Genomics, Immunogenetics and genomics, Linkage analysis and genetic mapping, Methods in Statistical Genetics, Molecular diagnostics, Mutation detection and analysis, Neurogenetics, Physical mapping and Population Genetics. Articles reporting animal models relevant to human biology or disease are also welcome. Preference will be given to those articles which address clinically relevant questions or which provide new insights into human biology. Unless reporting entirely novel and unusual aspects of a topic, clinical case reports, cytogenetic case reports, papers on descriptive population genetics, articles dealing with the frequency of polymorphisms or additional mutations within genes in which numerous lesions have already been described, and papers that report meta-analyses of previously published datasets will normally not be accepted. The Journal typically will not consider for publication manuscripts that report merely the isolation, map position, structure, and tissue expression profile of a gene of unknown function unless the gene is of particular interest or is a candidate gene involved in a human trait or disorder.