Sujoy Mukherjee , Ph.D.
Structure and Dynamics of Amyloid Fibrils and their pre-amyloidogenic states
One area of interest is the amyloid pathway where usually stable and soluble proteins have been found to convert into insoluble fibrils and deposit as amyloid plaques in various organs leading to so-called protein deposition diseases like the Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, prion diseases. Systemic amyloidosis refers to the condition where amyloid plaques are formed across multiple organs like the heart, kidney, lymph nodes, etc and a particularly dreadful form of this disease is the Amyloid Light chain (AL) amyloidosis. In addition to the deposition of wild type proteins in old age (SenileSystemic Amyloidosis), mutations can also render the proteins unstable, resulting in their deposition into amyloid plaques and causing familial type of amyloidosis like Familial Amyloid Polyneuropathy and Familial Amyloid Cardiomyopathy. We are using solution-state NMR spectroscopy to study the partially destabilized so-called invisible-states of these amyloidogenic proteins by which fibril formation is believed to be initiated and obtain atomic resolution information on residues that initiate protein aggregation. On the other hand, the structure of the amyloid fibrils are also being investigated using “magic-angle” spinning solid-state NMR.
Signal transduction by GPCRs: Study of structure, dynamics and ligand interaction
Another key interest area of our group is to understand the mechanism of signal transduction by G-protein coupled receoptors (GPCR). Because these are membrane proteins and very dynamic in nature, investigations into their structure and dynamics have eluded the scientific community by standard biophysical techniques. Solid state NMR using Cross-polarization with magic-angle spinning (CP-MAS) is a novel biophysical technique that can be used to investigate the structure, and more importantly, the dynamics of these membrane proteins.
* Postdoctoral Fellow (2008 – 2011) – The Ohio State University
* PhD (2008) – University of Illinois, Urbana-Champaign in Biophysics & Computational Biology
* B-Tech (2003) – I.I.T. Kharagpur in Biotechnology & Biochemical Engineering.
Patents & Publications
- Mahesh G, Jaiswal P, Dey S, Sengupta J, Mukherjee S. Cloning, expression, purification and characterization of oligomeric states of the native 5HT2A G-Protein-Coupled Receptor. Protein Pept Lett. 2018 Feb 6. doi: 10.2174/0929866525666180207110137. [Epub ahead of print]
- Mukherjee S, Pondaven SP, Hand K, Madine J, Jaroniec CP. Effect of amino acid mutations on the conformational dynamics of amyloidogenic immunoglobulin light-chains: A combined NMR and in silico study. Sci Rep. 2017 Sep 4;7(1):10339. doi: 10.1038/s41598-017-10906-w.
- Rasquinha JA, Bej A, Dutta S, Mukherjee S. Intrinsic Differences in Backbone Dynamics between Wild Type and DNA-Contact Mutants of the p53 DNA Binding Domain Revealed by Nuclear Magnetic Resonance Spectroscopy. Biochemistry. 2017 Sep 19;56(37):4962-4971. doi: 10.1021/acs.biochem.7b00514. Epub 2017 Sep 7.
- Mishra P, Choudhary S, Mukherjee S, Sengupta D, Sharma S, Hosur RV. Molten globule nature of Plasmodium falciparum P2 homo-tetramer. Biochem Biophys Rep. 2015 Mar 30;1:97-107. doi: 10.1016/j.bbrep.2015.03.010. eCollection 2015 May.
- Das, J. K.; Mall, S. S.; Bej, A.; Mukherjee, S., Conformational Flexibility Tunes the Propensity of Transthyretin to Form Fibrils Through Non-Native Intermediate States. Angew Chem Int Ed (Engl) (Early View, http://onlinelibrary.wiley.com/doi/10.1002/anie.201407323/abstract)
Mukherjee, S.; Pondaven, S. P.; Jaroniec, C. P., Conformational Flexibility of a Human Immunoglobulin Light Chain Variable Domain by Relaxation Dispersion Nuclear Magnetic Resonance Spectroscopy: Implications for Protein Misfolding and Amyloid Assembly Biochemistry 2011, 50, 5845-5857.
Mukherjee, S.; Huang, C.; Guerra, F.; Wang, K.; Oldfield, E., Thermodynamics of Bisphosphonates Binding to Human Bone: A Two-Site Model. J. Am. Chem. Soc. 2009, 131, (24), 8374-8375.
Mukherjee, S.; Song, Y.; Oldfield, E., NMR Investigations of the Static and Dynamic Structures of Bisphosphonates on Bone: a Molecular Model. J. Am. Chem. Soc.2008, 130, (4), 1264-1273.
Mao, J. H.; Mukherjee, S.; Zhang, Y.; Cao, R.; Sanders, J. M.; Song, Y. C.; Zhang, Y. H.; Meints, G. A.; Gao, Y. G.; Mukkamala, D.; Hudock, M. P.; Oldfield, E., Solid-state NMR, crystallographic, and computational investigation of Bisphosphonates and farnesyl diphosphate synthase-bisphosphonate complexes. J. Am. Chem. Soc. 2006, 128, (45), 14485-1449.