Structural characterization of the fusion core in syncytin, envelope protein of human endogenous retrovirus family W.
Syncytin is a captive retroviral envelope protein, possibly involved in the formation of the placental syncytiotrophoblast layer generated by trophoblast cell fusion at the maternal-fetal interface. We found that syncytin and type I viral envelope proteins shared similar structural profiling, especially in the regions of N- and C-terminal heptad repeats (NHR and CHR). We expressed the predicted regions of NHR (41aa) and CHR (34aa) in syncytin as a native single chain (named 2-helix protein) to characterize it. 2-Helix protein exists as a trimer and is highly alpha-helix, thermo-stable, and denatured by low pH. NHR and CHR could form a protease-resistant complex. The complex structure built by the molecular docking demonstrated that NHR and CHR associated in an antiparallel manner. Overall, the 2-helix protein could form a thermo-stable coiled coil trimer. The fusion core structure of syncytin was first demonstrated in endogenous retrovirus. These results support the explanation how syncytin mediates cytotrophoblast cell fusion involved in placental morphogenesis.
Gong
Rui
R
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Peng
Xiaoxue
X
Kang
Shuli
S
Feng
Huixing
H
Huang
Jianying
J
Zhang
Wentao
W
Lin
Donghai
D
Tien
Po
P
Xiao
Gengfu
G
D000595:Amino Acid Sequence; D001483:Base Sequence; D002942:Circular Dichroism; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D020077:Endogenous Retroviruses / Q000378:metabolism*; D015686:Gene Products, env / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D019302:HIV Envelope Protein gp160 / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011257:Pregnancy Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D011257:Pregnancy Proteins; C405335:syncytin