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Structural Biology 2018 & STD AIDS 2018
Journal of Genetics and Molecular Biology
|
Volume 2
S e p t e m b e r 0 3 - 0 4 , 2 0 1 8 | B a n g k o k , T h a i l a n d
allied
academies
STD-AIDS AND INFECTIOUS DISEASES
STRUCTURAL BIOLOGY AND PROTEOMICS
&
International Conference on
International Conference on
Joint Event on
B K C Chow, J Genet Mol Biol 2018, Volume 2
STRUCTURAL CO-EVOLUTION OF
PACAP/GCGR FROM INVERTEBRATES TO
VERTEBRATES
B K C Chow
The University of Hong Kong, China
Statement of the Problem:
G-protein coupled receptors (GPCRs), an essential
molecular signaling device to connect extracellular stimulus and intracellular
response, are currently one of the major targets for therapeutic drugs. Class B
GPCRsarehighlyattractivetherapeutictargetswithseveralpathophysiological
functions. In recent years, crystal structures of two full receptors (glucagon
receptor and CRF receptor) and several other extracellular domains were
released, enabling novel understanding of the interactions of this family of
ligand-receptor at atomic level. The current knowledge base provides great
opportunity to conduct comparative study and investigate the structural
evolution of the receptor family by generating reliable homology model of
class B1 GPCRs from various species. The comparison between primitive
and advanced species provide insight into how communicating systems are
built to support complicated operation of multiple tissues. Investigating these
GPCRs with long evolutionary history can provide treasurable information
for drug design. We intend to investigate the molecular evolution of class
B1 GPCRs from structural perspective, with focus on ligand binding pocket.
Comparative study of class B1 GPCRs has been a research focus of our lab
for more than 10 years.
Methodology & Theoretical Orientation:
We used data mining and
bioinformatics analysis along with molecular cloning techniques to develop
and clone ancestral PACAP/GCG receptor by using the information from
the genome projects to isolate all putative ligand and receptor cDNAs from
B floridae
and
B belcheri
and further screen the receptor sequences from
amphioxus. In quest to understand the pre-2WGD condition of PACAP and
GCG receptor interaction with their receptor, we developed a photo-label
probe analog to natural peptide, to test for the binding location on to the
receptor. To understand and compare the structure of primitive receptor
with the human receptors, we designed homology model of the receptor and
further developed a receptor ligand complex. This complex will be validated
by photoaffinity data provided by the help of photo labeled probe.
Conclusion&Significance:
InvestigatingGPCRswith long evolutionary history
by comparative approach will allow assessment of ligand binding domain of
the receptor for intracellular signaling, which is a treasurable information.
B K C Chow is a Chair Professor of the University of
Hong Kong. He has his research interest in endocri-
nology of brain-gut peptides, pleiotropic activities of
secretin in our body and evolution of GHRH/PACAP
peptides and receptors.
bkcc@hku.hkBIOGRAPHY
Figure.1: Summary of molecular cloning of
class B1 GPCRs and cognate ligands done by
our group. Each red stars * indicate sequence
reported in our publications.
Recent Publications
1. Ng SY (2012) Agnathan VIP, PACAP and their
receptors: ancestral origins of today’s highly
diversified forms. PLoS One 7: e44691.
2. Ng SY (2011) Discovery of a new
reproductive hormone in teleosts: pituitary
adenylate cyclase-activating polypeptide-
related peptide (PRP). Gen Comp Endocrinol
173: 405-410.