Mechanistic Basis of Propofol-Induced Disruption of Kinesin Processivity
Dr. Mandira Dutta pursued her Ph.D. at the Indian Association for the Cultivation of Science (IACS), Kolkata, India, under the supervision of Dr. Biman Jana. Her Ph.D. work focused on the theoretical and computational investigation of molecular motor dynamics and their effects on disease-related mutations. She obtained her Ph.D. degree in 2020 and is currently working as a postdoctoral research scholar in the group of Prof. Gregory A. Voth at the University of Chicago, USA. Her present research investigates the molecular mechanism of viral dynamics, especially SARS-CoV-2, using molecular dynamics simulations.
In this interview, she talks about her first-author publication titled “Mechanistic basis of propofol-induced disruption of kinesin processivity”, published in Proceedings of the National Academy of Sciences (PNAS), 2021.
How would you explain your paper’s key results to the non-scientific community?
We are all familiar with the term ‘anesthesia’, often experienced during surgeries. Propofol is a commonly used intravenous sedative for inducing and maintaining anesthesia. Another key concept is motor proteins—specialized proteins like dynein, kinesin, and myosin—that function as vehicles within our body to transport essential cellular cargo such as neurotransmitters, synaptic vesicles, and neurotrophic receptors.
Our study shows that propofol impairs the proper functioning of kinesin motor proteins, which in turn disrupts the transmission of neuronal signals, leading to loss of consciousness in patients.
Our study provides a general idea about the mechanisms of anesthetic agents on motor proteins.
What are the possible consequences of these findings for your research area?
Motor proteins maintain a unique “stress-strain” relationship for their movement. In kinesin, this involves an asymmetric strain between its two heads, which is crucial for its forward walking motion along microtubules. Propofol disrupts this asymmetry, effectively inhibiting kinesin’s forward motion and its signal transmission capabilities.
This study offers new molecular insights into how anesthetics like propofol impact motor proteins, potentially influencing future anesthetic drug development and neurobiology research.
What was the exciting moment (eureka moment) during your research?
The most exciting moment came when we observed that propofol disrupts the asymmetric strain between kinesin’s two heads, which is a key requirement for its movement. From earlier studies, we knew that the front head typically bears more strain than the rear one. Discovering that propofol inhibits this natural tension mechanism, and thereby kinesin’s processivity, was a breakthrough—especially as our study was the first to provide a molecular explanation for this phenomenon.
What do you hope to do next?
There’s much more to explore. Motor proteins form a complex and vast system. While our study provides insights into how propofol disrupts kinesin function, how this disruption translates to neuronal signal inhibition in the body remains unclear. Further studies are needed to understand propofol’s effects on other motor proteins like dynein and myosin.
Where do you seek scientific inspiration?
“Nothing in life is to be feared; it is only to be understood. Now is the time to understand more, so that we may fear less.” – Marie Curie
Understanding things at their molecular roots always inspires me. Biological systems are astonishingly complex, yet they operate in a synchronized and orderly fashion. This curiosity led me to pursue computational biophysics.
I am especially grateful to my Ph.D. advisor Dr. Biman Jana, whose mentorship helped shape my vision and focus my energy in the right direction.
How do you intend to help Indian science improve?
Science is a collective endeavor that drives humanity’s progress. I aim to inspire young minds in India to pursue research and foster scientific curiosity. Through my biophysics research focused on disease mechanisms—be it motor protein-related diseases or viral dynamics like SARS-CoV-2—I hope to contribute meaningfully to society.
Reference
M. Dutta, S. P. Gilbert, J. N. Onuchic, and B. Jana,
Mechanistic basis of propofol-induced disruption of kinesin processivity,
Proceedings of the National Academy of Sciences (PNAS), 2021, 118 (5): e2023659118.
DOI: 10.1073/pnas.2023659118
Edited by: Manveen K Sethi (Volunteer, Bio Patrika)
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