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Tryptophan-dependent membrane interaction and heteromerization with the internal fusion peptide by the membrane proximal external region of SARS-CoV spike protein

หน่วยงาน Nanyang Technological University, Singapore

รายละเอียด

ชื่อเรื่อง : Tryptophan-dependent membrane interaction and heteromerization with the internal fusion peptide by the membrane proximal external region of SARS-CoV spike protein
นักวิจัย : Liao, Ying , Zhang, Si Min , Neo, Tuan Ling , Tam, James P.
คำค้น : DRNTU::Science::Biological sciences::Biochemistry
หน่วยงาน : Nanyang Technological University, Singapore
ผู้ร่วมงาน : -
ปีพิมพ์ : 2558
อ้างอิง : Liao, Y., Zhang, S. M., Neo, T. L., & Tam, J. P. (2015). Tryptophan-dependent membrane interaction and heteromerization with the internal fusion peptide by the membrane proximal external region of SARS-CoV spike protein. Biochemistry, 54(9), 1819-1830. , http://hdl.handle.net/10220/25245 , http://dx.doi.org/10.1021/bi501352u
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : Biochemistry
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

The spike (S) protein of severe acute respiratory syndrome-associated CoV (SARS-CoV) mediates membrane fusion and viral entry. These events involve structural rearrangements, including heteromerization between two heptad repeats (HR1 and HR2) to form a trimer of dimers as a six-helix bundle (6-HB), a quaternary protein structure that brings two distant clusters of hydrophobic sequences into the proximity of each other, the internal fusion peptide (IFP) preceding HR1, and the highly conserved tryptophan (Trp)-rich membrane proximal external region (MPER) following HR2. Here, we show that MPER can undergo self-oligomerization and heteromerization with IFP, events that are Trp-dependent. To delineate the roles of Trp residues of MPER in forming these quaternary structures and interacting with membranes, we employed a panel of synthetic peptides: MPER peptide (M-wt) and its alanine (Ala) and phenylalanine (Phe) analogues. Ala substitutions of Trp inhibited its association with cellular membranes. Chemical cross-linking experiments showed that M-wt can self-interact to form oligomers and cross-interact with IFP23, a synthetic IFP peptide, to form a heterohexamer. In comparison, little high-order oligomer was formed between M-wt and fusion peptide. The specific interaction between M-wt and IFP23 was confirmed by immunofluorescence staining experiments. In aqueous solutions, both M-wt and IFP23 displayed random secondary structures that became helical in hydrophobic solvents. Triple-Ala substitutions of Trp in M-wt, but not the corresponding triple-Phe analogue, disrupted oligomerization of M-wt and hetero-oligomerization of M-wt with IFP23. Overall, our results show that Trp residues of MPER play a key role in maintaining the structure and functions of MPER, allowing it to interact with IFP to form a MPER–IFP heteromer, a putative quaternary structure extending from the 6-HB, and function in membrane fusion. Finally, we showed that a MPER peptide could serve as an inhibitor in the entry process.

NRF (Natl Research Foundation, S’pore)

บรรณานุกรม :
Liao, Ying , Zhang, Si Min , Neo, Tuan Ling , Tam, James P. . (2558). Tryptophan-dependent membrane interaction and heteromerization with the internal fusion peptide by the membrane proximal external region of SARS-CoV spike protein.
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Liao, Ying , Zhang, Si Min , Neo, Tuan Ling , Tam, James P. . 2558. "Tryptophan-dependent membrane interaction and heteromerization with the internal fusion peptide by the membrane proximal external region of SARS-CoV spike protein".
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Liao, Ying , Zhang, Si Min , Neo, Tuan Ling , Tam, James P. . "Tryptophan-dependent membrane interaction and heteromerization with the internal fusion peptide by the membrane proximal external region of SARS-CoV spike protein."
    กรุงเทพมหานคร : Nanyang Technological University, Singapore, 2558. Print.
Liao, Ying , Zhang, Si Min , Neo, Tuan Ling , Tam, James P. . Tryptophan-dependent membrane interaction and heteromerization with the internal fusion peptide by the membrane proximal external region of SARS-CoV spike protein. กรุงเทพมหานคร : Nanyang Technological University, Singapore; 2558.