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Dergiler / Türk Biyokimya Dergisi / 2021 / Cilt: 46 - Sayı: 2

Mutations in the SARS CoV-2 spike protein may cause functional changes in the protein quaternary structure

SARS CoV-2 spike proteinindeki mutasyonlar, protein kuaterner yapısında fonksiyonel değişikliklere neden olabilir

Ekrem AKBULUT
Sayfa
137–144
DOI
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Conclusions: It has been considered that SARS CoV-2 S glycoprotein mutations may cause changes in a protein functional structure that can affect the severity of disease.

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Amaç & Hipotez:Objectives: This study aimed to model the changes result ing from mutations in surface (spike/S) glycoproteins, which play a key role in the entry of the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) into host cells, in a protein quaternary structure and to evaluate their possible effects on the functional structure.
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Temel Bulgular & Veri:Methods: Genome sequence information of SARS CoV 2-infected patients located in Turkey was obtained from the GISAID EpiCoV database.
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Sonuç & Katkı:Conclusions: It has been considered that SARS CoV-2 S glycoprotein mutations may cause changes in a protein functional structure that can affect the severity of disease.
🔬Tür:Modelleme & Sayısal Simülasyon
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Alan Parametreleri

Özet

Objectives: This study aimed to model the changes result ing from mutations in surface (spike/S) glycoproteins, which play a key role in the entry of the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) into host cells, in a protein quaternary structure and to evaluate their possible effects on the functional structure. Methods: Genome sequence information of SARS CoV 2-infected patients located in Turkey was obtained from the GISAID EpiCoV database. Structural analysis of spike proteins was done using bioinformatics tools (MAFFT, PSIPRED, ProMod3, PyMoL and DynOmics). Results: We identified 76 Thr>Ile mutations in the N-ter minal domain; 468 Ile>Val mutations in the receptor bind ing site and 614 Asp>Gly, 679 Asn>Lys, 771 Ala>Val and 772 Val>Ile mutations in the S1 subunit. It has been observed that the mutations, except those of residues 771 and 772, may cause significant conformational, topological and electro static changes in a protein quaternary structure. It has been determined that the mutations in the receptor binding site transform the protein structure into a formation that can mask the binding site and affect receptor affinity. Conclusions: It has been considered that SARS CoV-2 S glycoprotein mutations may cause changes in a protein functional structure that can affect the severity of disease.

Abstract

Amaç: Bu çalışmada, şiddetli akut solunum sendromu koronavirüsü-2′nin (SARS CoV-2) konakçı hücrelere giri şinde anahtar rol oynayan yüzey (spike/S) glikoproteini, mutasyonların proteinin kuaterner ve fonksiyonel yapısı üzerindeki olası etkilerini değerlendirmek amacı ile modellendi. Gereç ve yöntem: Türkiye’de yerleşik SARS CoV-2 ile enfekte hastaların genom sekans bilgileri GISAID EpiCoV veri tabanından elde edildi. Spike proteinlerin yapısal ana lizi biyoinformatik araçlar (MAFFT, PSIPRED, ProMod3, PyMoL ve DynOmics) kullanılarak yapıldı. Tartışma: N-terminal bölgesinde 76 Thr>Ile, reseptör bağ lanma bölgesinde 468 Ile>Val, S1 alt biriminde 614 Asp>Gly, 679 Asn>Lys, 771 Ala>Val ve 772 Val>Ile mutasyonlarını tanımladık. 771 ve 772 rezidüleri dışındaki mutasyonların, protein kuaterner yapısında önemli konformasyonel, topo lojik ve elektrostatik değişikliklere neden olabileceği göz lenmiştir. Reseptör bağlanma bölgesindeki mutasyonların, protein yapısını, bağlanma sahasını maskeleyebilecek ve reseptör afinitesini etkileyebilecek bir formasyona dönüştürdüğü belirlenmiştir. Sonuç: SARS CoV-2 S glikoprotein mutasyonlarının, pro tein fonksiyonel yapısında hastalık şiddetini etkileyebile cek değişikliklere neden olabileceği düşünülmektedir.

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Bu Makaleye Atıf Yap

AKBULUT, E. (2021). Mutations in the SARS CoV-2 spike protein may cause functional changes in the protein quaternary structure. Türk Biyokimya Dergisi, Cilt: 46 - Sayı: 2, 137–144. https://ajindex.com/articles/394974

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