C O N P S
The fusion core of the Spike (S) protein is shown to the left. It is comprised of the two heptad repeat regions (HR) found within the S2 subunit of the S protein (Xu et al., 2004).
The two heptad repeat regions are called heptad repeat region 1 (HR1) and heptad repeat region 2 (HR2), or HR-N and HR-C to denote the closest terminus to the HR (Rota et al., 2003; Xu et al., 2004).
Click here to see the HR1 depicted in blue and HR2 depicted in yellow
The HRs are trimers that are collectively called the fusion core (Xu et al., 2004). The Fusion core is made of the six helices (three from HR1 and three from HR2) of the heptad repeat regions. Click here to see the three chains of each heptad repeat regions labeled . HR1 contains chains A, B, and C, which are colored blue, Tarheel blue, and cyan respictively . HR2 contains chains D, E, and F; colored neon green, yellow, and orange respectively (Xu et al., 2004).
The trimeric HR1 structure forms a parallel coiled-coil structure. Take a look at HR1 without HR2 shown
. The helices of HR2 relative to HR1 are in an antiparallel orientation. Now take a look at HR2 without HR1 shown
(Xu et al., 2004).
The trimers of each HR can be further divided into smaller units. Each of the three chains of the trimers is made up of two helices, forming a paired coiled-coil trimer. Click here to view two helices that comprise each chain of the two trimers (Xu et al., 2004). The ribbon structure of the two trimers illustrates the left-handed turn of the chains within each trimer. The chains are colored the same as above.
The coiled-coil structure of the trimers creates hydrophobic grooves in the side of trimer. HR2 uses the grooves in HR1 to pack tightly with it (Supekar, et al., 2004). Click here to see the HR1 and HR2 packed together . The hydrophobic regions of the trimers are shown as red spacefilled structure, while the hydrophillic regions have been changed to wireframe structures for clarity.
The HR1 and HR2 are separated by approximately 140 amino acids called the interhelical domain, which is not shown in this image (Tripet et al., 2004). There are numerous amino acids that interact between the HR1 trimer and HR2 trimer. Amino acids 916-950 of HR1 interact with amino acids 1151-1185 in HR2. Click here to view amino acids 916-950 (change from yellow to white in color) and 1151-1185 ( change from blue to white in color) . More specifically, there are four Valines --two from chain B of HR1 and two from chain F of HR2--that interact strongly between the two heptad regions. Click here to see the two Valines from chain B (purple) bind to the two valines from chain F (violet) (Tripet et al., 2004).
Rota, P. et al. 2003. Characterisation of a novel Coronavirus associated with Severe Acute Respiratory Syndrome. Science 300: 1394-1399.
Supekar, V. Bruckman, C. ,Ingallinella, P., Bianchi, E. Pessi, A., Cafri, A. 2004. Structure of a proteolytically resistant core from the sever acute respitratory syndrome coronavirus S2 fusion protein. PNAS 101(52): 17958-17963.
Tripet, B., Howard, M., Jobling, M., Holmes, R., Holmes, K., and Hodges, R. 2004. Structural characterization of the SARS-Coronavirus Spike S fusion protein core. The Journal of Biological Chemistry 279(20): 20836-20849.
Xu, Y., Lou, Z., Liu, Y. Pang, H., Tien, P., Gao, G., adn Rao, Z. 2004. Crystal structure of Severe Acute Respiratory Syndrome Coronavirus Spike protein fusion core. The Journal of Biological Chemistry 279 (47): 49414-49419.