Elucidation of structure-function relationships in small heat shock proteins and its importance in human diseases using biophysical methods
Small heat shock proteins (sHsps) exhibit molecular chaperone function and the molecular chaperone function and structure plays a vital role in various diseases. Mainly, my research deals with two small heat shock proteins i.e. Mycobacterium tuberculosis Hsp16.3 and lens α-crystallin. The chaperone function of Hsp16.3 is believed to play a crucial role in the survival of Mycobacterium tuberculosis pathogen inside the host.
Each of these small heat shock proteins possesses three distinct domains (N-terminal, α-crystallin and C-terminal). All these three domains play an important role in preserving the structure and chaperone function of these sHsps. In the last few years, I have carried out my research work to understand the role of C-terminal region of Hsp16.3 on the structure and chaperone function of this small heat shock protein by employing site directed mutagenesis and biophysical methods. Overall, our study suggests a ‘new structural element’ in the C-terminal region, i.e. the C-terminal extension, which plays an important role in the oligomerization, subunit exchange dynamics and chaperone function of Hsp16.3. FEBS Journal, 284, 277-300. (2017)
Eye lens is a vital organ in humans. The lens is majorly composed of crystallin proteins i.e. α-, β- and γ-crystallins. The turnover of these crystallin proteins is minimal in lens and hence the structural integrity and the functionality of these proteins need to be preserved in order to maintain the transparency of the lens. Aging and disease such as diabetes, often lead to various post translational modifications (PTMs) such as glycation, acetylation, truncation etc, in these crystallin proteins. These PTMs are quite capable enough to modulate the structure and functions of these crystallin proteins which may lead to the development of lens opacity termed as cataract.
My research specifically deals with two PTMs i.e. glycation and acetylation of these crystallin proteins. In the last few years, I have worked on the role of lysine acetylation on the structure and function of α- crystallin. In α-crystallin and we have found that acetylation enhances the chaperone function of this protein. Biochimica et Biophysica Acta-Molecular Basis of Disease, 1822, 120-129 (2012)Apart from this we have also shown that glycation by methyl glyoxal also enhances the chaperone function of α-crystallin PLoS One, 7, e30257 (2012). Therefore, acetylation and glycation may play a vital role in maintaining transparency of the lens by preserving the solubility and functionality of the crystallin proteins. Understanding the effect of these PTMs on the structure and function of lens crystallins will help us to develop new strategies to delay the onset of the cataract.
Elucidating the mechanism of interaction of metal complexes (anti-cancer agents) with DNA and proteins using biochemical techniques
Many transition metal complexes find applications in photodynamic therapy to cure diseases such as cancer etc. The interaction of these complexes with DNA and albumin proteins is vital in order to understand their pharmacological behaviour. My research focuses on understanding the strength and the mode of interaction of these complexes with DNA and albumin proteins by various biochemical and spectroscopic techniques. We have recently determined the photonuclease activity and mechanism of interaction with DNA and albumin proteins for a selected group of newly synthesized vanadium Dalton Transactions, 45, 18292-18307 (2016) and copper Dalton Transactions, 44(13), 6140-6157 (2015)complexes.