The Importance of ACTN3 R577X Polymorphism in Athletic Performance and Modeling of R577X Mutant Type and Wild Type ACTN3 Protein by Bioinformatics Analysis
Öz
ACTN3 R577X polimorfizmi ile atletik performans arasındaki ilişki üzerine yapılan çalışmalarda atletik performansın poligenik olduğu bilinmekle birlikte en hassas ilişkinin ACTN3 geni tarafından sağlandığı belirtilmektedir. Sonuçlar göz önüne alındığında, wild tip ve R577X arasında konformasyonel fark çok daha azdır (<0,05 A). R577X, wild tipten daha az amino aside (324 amino asit) sahiptir. R577X modelinin alt birimlerinin 4 uzun ve 5 kısa alfa-sarmal eğriye sahip olmadığı görülmüştür. Fiziko-kimya özelliklerinin analiz sonuçlarına göre, her model alifatik indekse çok yakındır, ancak R577X mutant tipi, wild tipten daha yüksektir. Her model çok sayıda hidrofilik amino asit içerir. R577 mutant tipinin wild tipten daha hidrofilik olduğu bulundu. Her model, negatif amino asitlere karşı daha olası amino asitlere sahiptir. Bununla birlikte, R577X mutant tipinin, wild tipten daha olası olduğu düşünülmektedir. Bu çalışmanın amacı; Wild tip ACTN geni ile R577X mutasyon bölgesi arasındaki fiziko ve kimya özelliklerini 3 boyutlu homoloji ile açıklamak ve homoloji modelleri yaparak bu konuda ileride yapılacak çalışmalara katkı sağlamaktır. Biyoinformatik bağlantı olarak Uniprot, Swiss Model ve Chimera kullanılmıştır. Sonuçlarımız, moleküler yapıda önemli bir değişiklik olmadığını, bu durumda proteinin işlevinin bozulmadığını gösterdi. Ancak yoğun kas performanslarının sonunda bu mutasyona sahip sporcular kas hasarına daha duyarlıdır. ACTN3'ün R577X mutant ve wild tip proteininin , Türkiye'de ilk kez üç boyutlu homoloji modeli ile fiziko-kimyasal özellikleri gösterildi.
Anahtar Kelimeler
Kaynakça
- Belli, T., Crisp, A.H., Verlengia, R., (2017). Greater muscle damage in athletes with ACTN3 R577X (RS1815739) gene polymorphism after an ultra-endurance race: a pilot study. Biol Sport. DOI: 10.5114/biolsport.2017.64583.
- Bulgay, C., Cetin, E, Orhan, O., Ergun, M., (2020). The Effects of The ACTN3 and ACE Genes on the Athletic Performance of Runners, Inonu University, Journal of Physical Education and Sport Sciences (IUJPESS), 7(1), 1-12 e-ISSN: 2148-6786
- Cięszczyk, P., Eider, J., Ostanek, M., Arczewska, A., Leońska-Duniec, A., Sawczyn, S., Ficek, K., Krupecki, K., (2011). Association of the ACTN3 R577X Polymorphism in Polish Power-Orientated Athletes. J Hum Kinet., 55-61. DOI: 10.2478/v10078-011-0022-0
- Del Coso, J., Moreno, V., Gutiérrez-Hellín, J., Baltazar-Martins, G., Ruíz-Moreno, C., Aguilar-Navarro, M., Lara, B., Lucía, A., (2019). ACTN3 R577X Genotype and Exercise Phenotypes in Recreational Marathon Runners. Genes, 10(6), 413. DOI:10.3390/genes10060413
- Delmonico, M.J., Zmuda, J.M., Taylor, B.C., Cauley, J.A., Harris, T.B., Manini, T.M., Schwartz, A., Li, R., Roth, S.M., Hurley, B.F., Bauer, D.C., Ferrell, R.E., Newman, A.B., (2008). Association of the ACTN3 Genotype and Physical Functioning. With Age in Older Adults. J Gerontol A Biol Sci Med Sci. 63:1227-1234.
- Dill, K.A., (1990). Dominant forces in protein folding. Biochemistry, 31:7134- 7155.
- Expasy: SIB Swiss Institute of Bioinformatics, ProtParam tool, https://web.expasy.org/protparam/,2021
- Franzot, G., Sjöblom, B., Gautel, M., Djinović Carugo, K., (2005). The crystal structure of the actin binding domain from alpha-actinin in its closed conformation: structural insight into phospholipid regulation of alpha-actinin. J Mol Biol. 348(1):151-65. DOI:10.1016/j.jmb.2005.01.002.
- Jones, D. T., (1999). Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol.
- Kaman, T., Kapici S., Sercan, C., Konuk, M., Ulucan, K., (2017). Determination of Alpha-Aktin-3 R577X Polymorphism Distribution in Turkish National Cyclists. Marmara University Journal of Sport Sciences. 2536-5150 DOI: 10.22396 / sbd.2017.24.
- Kikuchi, N., Tsuchiya Y., Nakazato K., Ishii N., Ochi E., (2017). Effects of the ACTN3 R577X Genotype on the Muscular Strength and Range of Motion Before and After Eccentric Contractions of the Elbow Flexors. Int J Sports Med, DOI:10.1055/s-0043-120762.
- Massidda, M., Bachis, V., Corrias, L., Piras, F., Scorcu, M., Culigioni, C., Masala, D., Calò, C.M., (2015). ACTN3 R577X polymorphism is not associated with team sport athletic status in Italians. Sports Medicine.
- Mutlucan, H., Biyikli, T., Eken, B.F., Sercan, C., Kapici, S., Ulucan, K., (2017). Investigation of Alfa-Aktin-3N R577 X Polymorphism in Turkish Professional Football Players. Marmara University Journal of Sport Sciences, 2536-5150. DOI: 10.22396 / sbd.2017.26.
- Oflaz, O., (2017). Homology based three dimensional structure modeling of AVPR2 protein Ofcan Oflaz.Hacettepe University / Institute of Science / Department of Biology. Thesis.2017.
- Oliveira, E.C., Rodrigues, P., Salgueirosa, F.M., Seniski, G.G., Wharton, L., Osiecki, R., (2018). Effect of ACTN3 R577X Genotypes on Muscle Strength and Power in Brazilian Mixed Martial Arts Athletes. Journal of Exercise Physiology online.
- Papadimitriou, I.D., Lockey, S.J., Voisin, S., Herbert, A.J., Garton, F., Houweling, P.J., Cieszczyk, P., Skrendo, A.M., Sawczuk, M., Massidda, M., Calò, C.M., Astratenkova, I.V., Kouvatsi, A., Druzhevskaya, A.M., Jacques, M., Ahmetov, I.I., Stebbings, G.K., Heffernan, S., Day, S.H., Erskine, R., Pedlar, C., Kipps, C., North, K.N., Williams, A.G. and Eynon, N., (2018). No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes. BMC Genomics. DOI: 10.1186/s12864-017-4412-0.
- Ruan, W, Lai, M. (2007). Actin, a reliable marker of internal control? Clin Chim Acta. 385:1-5. DOI: 10.1016/j.cca.2007.07.003.
- Seto, J.T., Quinlan, K.G., Lek, M., Zheng, X.F., Garton, F., MacArthur, D.G., Hogarth, M.W., Houweling, P.J., Gregorevic, P., Turner, N., Cooney, G.J., Yang, N., North, K.N., (2013). ACTN3 genotype influences muscle performance through the regulation of calcineurin signaling. J Clin Invest. 123(10):4255-63. DOI: 10.1172/JCI67691. Swiss-Model, https://swissmodel.expasy.org/, 2021
- Sanlisoy, F., Altıntas, N., Buyukyazi, G., Candan, N., (2011). Investigation of ACTN3 R577X genotype distribution of elite athletes from the Aegean region. Cumhuriyet Medical Journal 33: 153-159.
- Ulucan, K., (2016). ACTN3 R577X Polymorphism Literature Summary of Turkish Athletes in Terms of Sports Genetics. Clinical and Experimental Health Science. 6 (1): 44-7.
- UCSF Chimera, https://www.cgl.ucsf.edu/chimera/, 2021
- Yang, N., MacArthur, D.G., Gulbin, J.P., Hahn, A.G., Beggs, A.H., Easteal, S., North, K., (2003). ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet. 73(3):627-31. DOI: 10.1086/377590.
The Importance of ACTN3 R577X Polymorphism in Athletic Performance and Modeling of R577X Mutant Type and Wild Type ACTN3 Protein by Bioinformatics Analysis
Öz
In studies conducted on the relationship between ACTN3 R577X polymorphism and athletic performance, it is known that athletic performance is polygenic, but the most sensitive relationship is provided by the ACTN3 gene. Considering the results, the conformational difference is much less (<0.05 A) between wild type and R577X. R577X has fewer amino acids (324 amino acids) than the wild type. It has been observed that the subunits of the R577X model do not have 4 long and 5 short alpha-helical curves. According to the analysis results of physico-chemistry properties, each model is very close to alipatich endex, but the R577X mutant type is higher than the wild type. Each model contains a large number of hydrophilic amino acids. R577 was found to be more hydrophilic than wild type. Each model has more likely amino acids versus negative amino acids. However, it considers the R577X mutant type more likely than the wild type. The purpose of this study is; explaining physico and chemistry properties with 3D homology between the wild type of ACTN gene and the R577X mutation region and contributed to future studies on this subject by making homology models. Uniprot, Swiss Model and Chimera were used as bioinformatics transition. Our results showed that there was no significant change in the molecular structure, in which case the function of the protein was not impaired. However, athletes with this mutation at the end of intense muscle performances are more susceptible to muscle damage. R577X mutant and wild-type protein of ACTN3 the physico-chemical properties of three-dimensional homology model was performed for the first time in Turkey.
Anahtar Kelimeler
Kaynakça
- Belli, T., Crisp, A.H., Verlengia, R., (2017). Greater muscle damage in athletes with ACTN3 R577X (RS1815739) gene polymorphism after an ultra-endurance race: a pilot study. Biol Sport. DOI: 10.5114/biolsport.2017.64583.
- Bulgay, C., Cetin, E, Orhan, O., Ergun, M., (2020). The Effects of The ACTN3 and ACE Genes on the Athletic Performance of Runners, Inonu University, Journal of Physical Education and Sport Sciences (IUJPESS), 7(1), 1-12 e-ISSN: 2148-6786
- Cięszczyk, P., Eider, J., Ostanek, M., Arczewska, A., Leońska-Duniec, A., Sawczyn, S., Ficek, K., Krupecki, K., (2011). Association of the ACTN3 R577X Polymorphism in Polish Power-Orientated Athletes. J Hum Kinet., 55-61. DOI: 10.2478/v10078-011-0022-0
- Del Coso, J., Moreno, V., Gutiérrez-Hellín, J., Baltazar-Martins, G., Ruíz-Moreno, C., Aguilar-Navarro, M., Lara, B., Lucía, A., (2019). ACTN3 R577X Genotype and Exercise Phenotypes in Recreational Marathon Runners. Genes, 10(6), 413. DOI:10.3390/genes10060413
- Delmonico, M.J., Zmuda, J.M., Taylor, B.C., Cauley, J.A., Harris, T.B., Manini, T.M., Schwartz, A., Li, R., Roth, S.M., Hurley, B.F., Bauer, D.C., Ferrell, R.E., Newman, A.B., (2008). Association of the ACTN3 Genotype and Physical Functioning. With Age in Older Adults. J Gerontol A Biol Sci Med Sci. 63:1227-1234.
- Dill, K.A., (1990). Dominant forces in protein folding. Biochemistry, 31:7134- 7155.
- Expasy: SIB Swiss Institute of Bioinformatics, ProtParam tool, https://web.expasy.org/protparam/,2021
- Franzot, G., Sjöblom, B., Gautel, M., Djinović Carugo, K., (2005). The crystal structure of the actin binding domain from alpha-actinin in its closed conformation: structural insight into phospholipid regulation of alpha-actinin. J Mol Biol. 348(1):151-65. DOI:10.1016/j.jmb.2005.01.002.
- Jones, D. T., (1999). Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol.
- Kaman, T., Kapici S., Sercan, C., Konuk, M., Ulucan, K., (2017). Determination of Alpha-Aktin-3 R577X Polymorphism Distribution in Turkish National Cyclists. Marmara University Journal of Sport Sciences. 2536-5150 DOI: 10.22396 / sbd.2017.24.
- Kikuchi, N., Tsuchiya Y., Nakazato K., Ishii N., Ochi E., (2017). Effects of the ACTN3 R577X Genotype on the Muscular Strength and Range of Motion Before and After Eccentric Contractions of the Elbow Flexors. Int J Sports Med, DOI:10.1055/s-0043-120762.
- Massidda, M., Bachis, V., Corrias, L., Piras, F., Scorcu, M., Culigioni, C., Masala, D., Calò, C.M., (2015). ACTN3 R577X polymorphism is not associated with team sport athletic status in Italians. Sports Medicine.
- Mutlucan, H., Biyikli, T., Eken, B.F., Sercan, C., Kapici, S., Ulucan, K., (2017). Investigation of Alfa-Aktin-3N R577 X Polymorphism in Turkish Professional Football Players. Marmara University Journal of Sport Sciences, 2536-5150. DOI: 10.22396 / sbd.2017.26.
- Oflaz, O., (2017). Homology based three dimensional structure modeling of AVPR2 protein Ofcan Oflaz.Hacettepe University / Institute of Science / Department of Biology. Thesis.2017.
- Oliveira, E.C., Rodrigues, P., Salgueirosa, F.M., Seniski, G.G., Wharton, L., Osiecki, R., (2018). Effect of ACTN3 R577X Genotypes on Muscle Strength and Power in Brazilian Mixed Martial Arts Athletes. Journal of Exercise Physiology online.
- Papadimitriou, I.D., Lockey, S.J., Voisin, S., Herbert, A.J., Garton, F., Houweling, P.J., Cieszczyk, P., Skrendo, A.M., Sawczuk, M., Massidda, M., Calò, C.M., Astratenkova, I.V., Kouvatsi, A., Druzhevskaya, A.M., Jacques, M., Ahmetov, I.I., Stebbings, G.K., Heffernan, S., Day, S.H., Erskine, R., Pedlar, C., Kipps, C., North, K.N., Williams, A.G. and Eynon, N., (2018). No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes. BMC Genomics. DOI: 10.1186/s12864-017-4412-0.
- Ruan, W, Lai, M. (2007). Actin, a reliable marker of internal control? Clin Chim Acta. 385:1-5. DOI: 10.1016/j.cca.2007.07.003.
- Seto, J.T., Quinlan, K.G., Lek, M., Zheng, X.F., Garton, F., MacArthur, D.G., Hogarth, M.W., Houweling, P.J., Gregorevic, P., Turner, N., Cooney, G.J., Yang, N., North, K.N., (2013). ACTN3 genotype influences muscle performance through the regulation of calcineurin signaling. J Clin Invest. 123(10):4255-63. DOI: 10.1172/JCI67691. Swiss-Model, https://swissmodel.expasy.org/, 2021
- Sanlisoy, F., Altıntas, N., Buyukyazi, G., Candan, N., (2011). Investigation of ACTN3 R577X genotype distribution of elite athletes from the Aegean region. Cumhuriyet Medical Journal 33: 153-159.
- Ulucan, K., (2016). ACTN3 R577X Polymorphism Literature Summary of Turkish Athletes in Terms of Sports Genetics. Clinical and Experimental Health Science. 6 (1): 44-7.
- UCSF Chimera, https://www.cgl.ucsf.edu/chimera/, 2021
- Yang, N., MacArthur, D.G., Gulbin, J.P., Hahn, A.G., Beggs, A.H., Easteal, S., North, K., (2003). ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet. 73(3):627-31. DOI: 10.1086/377590.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Yayımlanma Tarihi | 26 Nisan 2021 |
| Yayımlandığı Sayı | Yıl 2021Cilt: 6 Sayı: 1 |
