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Structural Biophysics Section
Nico Tjandra, PhD, Principal Investigator
The main interest of the Structural Biophysics Section is to develop
new techniques in NMR to efficiently
study structure and dynamics of biomolecules. We are focused on
discovering the underlying basic physical principle that defines
some parameters that we observe with solution NMR. The intent is
to develop a protocol to apply this knowledge into structure determination.
In most of these parameters that we measure there are always some
dynamic components. One aspects of our research is to try to separate
the structural from the dynamic components of the NMR parameters.
The detail dynamic information that we obtain together with the
solution structure of the biomolecules completes the full picture
of the molecules in their physiological environment.
In addition we also utilize other biophysical techniques such as light scattering and imaging to gain
additional structural and cellular information on the molecules of interest. Our goal is to understand the
basic mechanism of protein interactions that govern various cellular processes.
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A stereo view of the superposition of the 20 lowest energy NMR structures of the N-terminal domain of the human T-cell leukemia virus type 1 (HTLV-1) Capsid protein. Helices are color coded. |
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Comparison of the N-terminal Capsid Protein of HIV-1 (green) and HTLV-1 (yellow). |
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Detail comparison of the AGPL/I motif in Capsid proteins. This motif is important for Cyclophilin A (Cyp A) binding to Hiv-1 Capsid. Cyp A does not bind HTLV-1 Capsid. The structural comparison shows that the HIV-1 P90 cis-trans isomerization and greater loop exposure facilitates Cyp A interaction. |
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Asp-Pro salt bridge stabilizes the orientation of the β-hairpin in the Capsid protein. A small difference in the salt bridge conformation leads to the overall change in the β-hairpin orientation. |
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Comparison of NMR structures of Bcl-2 family of proteins shows great similarity while their functions are exactly opposite. |
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Structural comparison of Bax and Bcl-xL + BH3 peptide reveals similar fold. The molecular interaction stabilizing the BH3 peptide in the hydrophobic pocket of Bcl-xL is also quite similar to the ones stabilizing helix a9 in Bax. Note the reverse orientation of the BH3 peptide in Bcl-xL hydrophobic pocket relative to the a9 helix in Bax. |
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Comparison of the N-terminal tail of the human and yeast Fis1 protein. The yeast Fis1 N-terminal sits in the hydrophobic groove of the protein. The hydrophobic interaction between the N-terminal tail and the groove is complemented by electrostatic interactions at the its perimeter. Truncation of this N-terminal tail abolishes Mdv1 recruitment to the mitochondria membrane, thus inhibiting mitochondria fission. This is illustrated by the diffuse profile of the GFP-Mdv1 confocal in yeast transfected with N-terminal truncated Fis1. |
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