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Structural Biology 2018
Volume: 4
Biochemistry & Molecular Biology Journal
Page 73
March 15-16 2018
Barcelona, Spain
10
th
Edition of International Conference on
Structural Biology
I
D3, a member of the ID multigene family of helix loop helix
domain can inhibit the regulation of transcription upon protein-
protein interaction. DNA binding inhibitor protein has long been
characterized as an oncogene that implicates its functional role
through its helix–loop–helix (HLH) structure. TCF4 protein which
is involved in the transcription regulation is inhibited by ID3 the
protein that lacks DNA domain. Our current work aims to identify
the functional and physical interaction of this proteins and
designing of an aptamer to prevent the interaction of TCF4 and
ID3. Network analysis has been performed to predict the inhibitor
for ID3. At present there isno threedimensional structureavailable
for these proteins which limits our understanding of its interacting
mechanism. We used
ab initio
method to build the model from
primary sequence. The stability of these proteins and peptide
were obtained through MD simulation at 30ns. The integration
of PCA and FEL were shown to be a very useful approaches to
gain an overall view of the conformational landscape accessible
to a protein and helped in the identification of the key residues
of TCF4 (Arg 567, Arg 515, Glu 587, Met 590, Gln 519) and ID3
(Glu 36, Asp 43, Cys 47, Arg 50, Arg 60) buried in their HLH
motifs which are responsible for dimerization process. All these
observations correlate with experimental reports, suggesting that
these key residues might play a crucial role in the regulation of
transcription and muscle specific genes and cellular signaling
pathways controlling proliferation. Thus, the study throws light on
the interacting mechanism of ID3-TCF4 and ID3-peptide (ID1/3-
PA7) complex and conformational space indicating the key
structural changes within the helical regions of the motif.
sikha.biotech@gmail.comInteracting mechanism of transcriptional inhibitor protein ID3
and TCF4 protein: molecular dynamics and docking approach
Sikha Morang, Ramadas Krishna, Nishith Saurav Topno
and
Guneswar Sethi
Pondicherry University, India
Biochem Mol biol J, Volume 4
DOI: 10.21767/2471-8084-C1-009