5
A P P L I C A T I O N N O T E
Exendin (9-39), a GLP1R antagonist, shows
therapeutic potential in various conditions. It
effectively raises blood glucose by inhibiting
excessive insulin secretion in Congenital Hy-
perinsulinism (CHI), offering hope for patients
unresponsive to standard therapies. Preclinical
studies suggest it may influence neuroprotec-
tive mechanisms, impacting synaptic transmis-
sion and memory through glutamate uptake
and astrocytic regulation. Additionally, Exendin
(9-39) has been explored as a probe for imaging
pancreatic beta-cells, aiding in understanding
pancreatic function and beta-cell distribution in
conditions like diabetes.
Membrane protein – Membrane protein interac-
tion: NTCP and LHBsAg
Hepatitis B Virus (HBV) infection is a major glob-
al health issue, leading to severe liver diseases
such as cirrhosis and hepatocellular carcinoma
(HCC) (17). The entry of HBV into hepatocytes is
mediated by the sodium taurocholate co-trans-
porting polypeptide (NTCP), which serves as a
receptor for the virus. This interaction occurs
specifically between NTCP and the large hepa-
titis B surface antigen (LHBsAg), facilitating viral
attachment and internalization (18). NTCP is a
transmembrane protein that primarily functions
as a bile acid transporter in the liver.
It contains several glycosylation sites that are
crucial for its stability, trafficking, and role in
HBV infection (19). The full-length structure of
NTCP has not yet been resolved, but its func-
tional domains involved in viral entry have
been characterized through mutational studies,
which indicate critical residues like tyrosine 146,
and are necessary for HBV binding and internal-
ization (20).
The large hepatitis B surface antigen (LHBsAg)
is a glycoprotein on the viral envelope that me-
diates the initial attachment to hepatocytes
through its pre-S1 domain. Although the full-
length structure of LHBsAg is not completely
solved, its interaction domains with NTCP have
been identified (21).
