Sequence–function correlation of the transmembrane domains in NS4B of HCV using a computational approach

Ta-Chou Huang; Wolfgang B. Fischer; Ta-Chou Huang; Wolfgang B. Fischer

doi:10.3934/biophy.2021013

AIMS Biophysics

2021, Volume 8, Issue 2: 165-181. doi: 10.3934/biophy.2021013

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Sequence–function correlation of the transmembrane domains in NS4B of HCV using a computational approach

Ta-Chou Huang ,
Wolfgang B. Fischer ^,

Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan

Received: 25 February 2021 Accepted: 13 April 2021 Published: 20 April 2021

An algorithm is applied to propose a sequence–function correlation of the transmembrane domains (TMDs) of the non-structural protein 4B (NS4B) of hepatitis C virus (HCV). The putative sequence of the TMDs is obtained using 20 available secondary structure prediction programs (SSPPs) with different lengths of the overall amino acid sequence of the protein as input. The results support the notion of four helical TMDs. Whilst the region of the first TMDs leaves room for speculation about an additional TMD, the other three TMDs are consistently predicted. Structural features and the role of each of the TMDs is proposed by applying pairwise sequence alignment using BLAST on the level (i) protein sequence alignment and consequent (ii) function-related alignment. Sequence identity with those TMDs of proteins involved in Ca-homeostasis and generation of replication vesicles, such as Nsp3 of corona viruses, murine coronavirus especially mouse hepatitis virus (MHV), middle east respiratory syndrome coronavirus (MERS), severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2, are suggested. Focusing the search on those proteins in particular and their TMDs playing an active role in their mechanism of function, such as transporters, pumps, viral channel forming protein Vpu of human immunodeficiency virus type 1 (HIV-1) and mediators, suggests TMDs 2 and 4 to have functional roles in NS4B, as well as additionally TMD1 and 3 in case of vesicle formation.
- secondary structure prediction,
- sequence alignment,
- structure–function correlation,
- bioinformatics,
- viral membrane protein,
- NS4B of HCV
Citation: Ta-Chou Huang, Wolfgang B. Fischer. Sequence–function correlation of the transmembrane domains in NS4B of HCV using a computational approach[J]. AIMS Biophysics, 2021, 8(2): 165-181. doi: 10.3934/biophy.2021013

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Abstract

An algorithm is applied to propose a sequence–function correlation of the transmembrane domains (TMDs) of the non-structural protein 4B (NS4B) of hepatitis C virus (HCV). The putative sequence of the TMDs is obtained using 20 available secondary structure prediction programs (SSPPs) with different lengths of the overall amino acid sequence of the protein as input. The results support the notion of four helical TMDs. Whilst the region of the first TMDs leaves room for speculation about an additional TMD, the other three TMDs are consistently predicted. Structural features and the role of each of the TMDs is proposed by applying pairwise sequence alignment using BLAST on the level (i) protein sequence alignment and consequent (ii) function-related alignment. Sequence identity with those TMDs of proteins involved in Ca-homeostasis and generation of replication vesicles, such as Nsp3 of corona viruses, murine coronavirus especially mouse hepatitis virus (MHV), middle east respiratory syndrome coronavirus (MERS), severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2, are suggested. Focusing the search on those proteins in particular and their TMDs playing an active role in their mechanism of function, such as transporters, pumps, viral channel forming protein Vpu of human immunodeficiency virus type 1 (HIV-1) and mediators, suggests TMDs 2 and 4 to have functional roles in NS4B, as well as additionally TMD1 and 3 in case of vesicle formation.

Acknowledgments

WBF thanks the Ministry of Science and Technology Taiwan (MOST-104-2112-M-010-001-MY3) for financial support. We are grateful to the National Center for High-performance Computing Taiwan for computer time and facilities.

Conflict of interest

The authors declare no conflict of interests.

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