Probing the structural impacts of arg388 replacements in pkp2 protein complex: spesific case in arvc

Kutlu, Aslı
Şahin, Şuara
Özkan, Mehmet Emre
Ulukaya, Engin
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is form of heart disease associated with removal of right ventricle by scar tissue that results in heart rhythm problems [1]. It is caused by a set of mutations existing in desmosomal proteins that are listed as desmoplakin (DP), plakophilin-2 (PKP2), desmoglein-2 (DSDG2), and desmocollin-2 (DSC2), and they are all involved in cell-to-cell adhesion [2]. Within the scope of this project, we focus on the 388th position of PKP2 protein since there exist 4 missense mutations, e.g., Arg388Trp, Arg388Pro, Arg388Gln and Arg388 Gly. Among these four variants, only Arg388Trp and Arg388Pro are reported as pathogenic to ARVC, and others remain as ‘VUS’. To understand more about disease mechanism caused by missense variants at 388th position of PKP2 protein as being either VUS or pathogenic, we performed 100 ns classical all-atom molecular dynamics (MD) simulations. Based on the results of MD simulations, we aimed to obtain more detailed information about Arg388Gln/Gly variants in terms of being pathogenic or not by comparing the structural features of native and mutant PKP2 proteins. The differences in intramolecular interactions with RMSD and Rg patterns of native and mutant protein structures demonstrated that the structural features of Arg388Trp and Arg388Pro were like those of Arg388Gly and Arg388Gln. The correlation coefficient analyses based on RMSD patterns of native and mutant protein structures validated the presence of structural alterations between Arg388Trp/Pro/Gly/Gln. By relying on the comparison of structural features of protein molecules, we concluded that Arg388Gly and Arg388Gln seem to be 'pathogenic' due to structural similarities with Arg388Trp and Arg388Pro.


Investigation of fluid structure interaction in cardiovascular system from diagnostic and pathological perspective
Salman, Hüseyin Enes; Yazıcıoğlu, Yiğit; Sert, Cüneyt; Department of Mechanical Engineering (2012)
Atherosclerosis is a disease of the cardiovascular system where a stenosis may develop in an artery which is an abnormal narrowing in the blood vessel that adversely affects the blood flow. Due to the constriction of the blood vessel, the flow is disturbed, forming a jet and recirculation downstream of the stenosis. Dynamic pressure fluctuations on the inner wall of the blood vessel leads to the vibration of the vessel structure and acoustic energy is propagated through the surrounding tissue that can be de...
Identification of Three Novel FBN1 Mutations and Their Phenotypic Relationship of Marfan Syndrome
KAYHAN, GÜLSÜM; ERGÜN, MEHMET ALİ; Ergun, Sezen Guntekin; KULA, SERDAR; PERÇİN, Ferda Emriye (Mary Ann Liebert Inc, 2018-07-26)
Background: Marfan syndrome (MS), a connective tissue disorder that affects ocular, skeletal, and cardiovascular systems, is caused by heterozygous pathogenic variants in FBN1. To date, over 1800 different pathogenic variants have been reported.
Analyzing the expression patterns of vitamin D metabolizing CYP27B1 and CYP24A1 in brain tissue of vitamin D treated mice with Multiple Sclerosis (MS)
Özdoğan, Dilara; Adalı, Orhan; Evin, Emre; Department of Molecular Biology and Genetics (2022-8)
The etiopathogenesis of Multiple Sclerosis (MS), an inflammatory demyelinating autoimmune disease of the central nervous system, is still unknown. MS is a complex, recurring, and frequently progressing condition. There is a hypothesis that MS is adversely associated with the length and intensity of sunlight exposure and vitamin D concentrations since MS frequency rises with increasing latitude. A female C57BL/6 mouse model for autoimmune encephalomyelitis (EAE) was used in this investigation to examine the ...
Solak, Damla; Adalı, Orhan; Department of Molecular Biology and Genetics (2023-1-27)
Multiple sclerosis (MS) is an autoimmune neurodegenerative disease which affects brain and spinal cord. Myelin which wraps around the axon and its progenitor cells, oligodendrocytes, are destroyed in this disease. This results in the loss of signal transmission which leads to axonal, and eventually neuronal loss. There are various symptoms of the disease such as unstable feelings, fatigue, visual disability, muscle spasms, and walking difficulties. The etiology of the disease is still in its infancy; howeve...
Generation and characterization of human induced pluripotent stem cell line METUi001-A from a 25-year-old male patient with relapsing-remitting multiple sclerosis
Koc, Dilara; Begentaş, Onur Can; Yurtogullari, Sukran; Temel, Musa; Akcali, Kamil Can; Demirkaya, Seref; Kiriş, Erkan (2021-05-01)
Multiple sclerosis is a chronic disease characterized by inflammation, demyelination, and axonal damage in the central nervous system. Here, we established an induced pluripotent stem cell (iPSC) line METUi001-A from the peripheral blood mononuclear cells of a 25-year-old male individual with clinically diagnosed Relapsing-Remitting Multiple Sclerosis (RRMS) using the integration-free Sendai reprogramming method. We demonstrated that the iPSCs are free of exogenous Sendai reprogramming vectors, have a norma...
Citation Formats
A. Kutlu, Ş. Şahin, M. E. Özkan, and E. Ulukaya, “Probing the structural impacts of arg388 replacements in pkp2 protein complex: spesific case in arvc,” Erdemli, Mersin, TÜRKİYE, 2022, p. 3062, Accessed: 00, 2023. [Online]. Available: