Passage 10: N Protein
The N protein is a structurally heterogeneous, 419-amino acid-long, multidomain RNA-binding protein. Like other coronaviruses, the N protein also has
two conserved, independently folded domains, namely the N-terminal domain
(NTD) and the C-terminal domain (CTD). These two domains are connected by an
inherently disordered region (IDR) called the central linking region (LKR). The LKR
includes a Ser/Arg (SR)-rich region, which contains putative phosphorylation sites.
In addition, there are two IDRs on both sides of the NTD and CTD, which are called
N-arm and C-tail. NTD is responsible for RNA binding, CTD is responsible for RNA
binding and dimerization, and IDR is responsible for regulating the RNA-binding
activity and oligomerization of NTD and CTD.
NTD takes the shape of a right-handed fist. It consists of a four-strand antiparallel
β-fold core subdomain. The N protein plays a key role in the viral life cycle by
binding to the viral RNA genome and packing it into a helical ribonucleocapsid
(RNP) complex. This process is crucial for the assembly of the viral particle and its
subsequent release from the host cell. This process is seen in Figure 1.
Many RNA-binding proteins, especially those with a high proportion of inherently
disordered regions, participate in liquid-liquid phase separation (LLPS). The protein
LLPS is a physical and chemical phenomenon that is considered to be the key
mechanism for organizing macromolecules, such as proteins and nucleic acids, into
membrane-free organelles. These membrane cell compartments are dynamically
assembled by LLPs and endow cells with the important ability to initiate biological
functions or responses to a range of pressures. After RNA virus infection, LLPS
mediates the formation of stress granules and P-bodies. These substances play an
important role in antiviral immunity by inhibiting the translation of viral mRNA and
promoting RNA degradation. LLPS is also considered to be the key to virus assembly.
What specific part of the virus would likely make contact with our immune
system?
A) The spike protein would attach to the variable region of antibodies
B) The spike protein would only attach to the light chain of the antibodies
C) The viral RNA would attach to the variable region of antibodies
D) The viral RNA would only attach to the heavy chain of antibodies
Correct answer: A. As the virus travels in the body, its RNA is
not exposed on the surface. Since the genetic code is sensitive, it will often be
protected inside of a protein coat and a viral capsid. Since the viral genetic code
is inside of the virus and not on the outside, it is very unlikely that the general
code itself will attach to the body’s immune system. Genetics often does not
approach the surface of the virus unless it is time for it to seminate throughout
a host cell. Although technically, there could be antibodies that can detect viral
genetic code; it is unlikely that that genetic code is circulating in our system for it
to attach to antibodies. Therefore, answer choices C and D are eliminated. Since the
antibody structure has two light chains and two heavy chains, both are involved in
producing the variable region. It is unlikely that solely the light chain or heavy chain
is responsible for attaching to pathogens. The area of the antibody that attaches
to pathogens is the variable region, and the constant region is similar for many
antibodies. The reason the variable is named such is because that is the area that is
highly differentiated in a variation of antibodies, allowing the body to detect many
different unique pathogens. The variable region is composed of both the light and
heavy chain, making answer choice A the best answer.
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