Research Groups

Mammalian Biology: Structural and Computational Biology

Research Interests and Description

Staff Research Scientist: Arulandu Arockiasamy, PhD

Group Leader: Amit Sharma

Group Members

Research Interests

Membrane proteins Metal-ion transport. Specialized protein secretion, type VII secretion system (T4SS). Mycobacteria and structural biology.

Description of Research

Structural Biology of Mycobacterial membrane proteins
We use atomic structures as a primary tool along with biochemical, biophysical and in vivo methods to understand a few essential biological processes. Our Group’s major focus is to understand the molecular mechanisms behind (a) metal-ion and (b) virulent protein translocation across inner membrane of Mycobacteria, in particular M. tb.
(a) Metal-ion uptake and efflux play a key role in intracellular parasitism and immunity, wherein it is crucial for both the pathogen and the host to effectively use metal-ions for their survival and advantage. Although Mycobacterial genomes code for several metal-ion transporters, experimental evidence on metal-ion selection, delivery, and import/export is lacking. Hence, a systematic approach is undertaken to study these putative transporters in vitro.
(b) The ESX secretion system (type VII secretion system -T7SS) is unique in Mycobacteria and the machine components are conserved in a few other Gram-positive bacterial pathogens as well. M. tb has successfully used these specialized protein section systems (ESX-1, ESX-3 and ESX-5) to its advantage to make a niche in the hostile intracellular environment. We aim to gain deeper insight into the basic mechanistic details of these molecular machines.
In addition to integral membrane proteins, we work on other challenging soluble proteins involved in various biological processes.

Publications

Kashyap, M., Jagga, Z., Das, B.K., Arockiasamy, A., Bhavesh, N.S. 2011. 1H, 13C and 15N NMR assignments of inactive form of P1 endolysin Lyz. Biomol NMR Assign In press PubMed link

Arockiasamy, A., Aggarwal, A., Savva, C.G., Holzenburg, A., Sacchettini, J.C. 2011. Crystal structure of calcium dodecin (Rv0379), from Mycobacterium tuberculosis with a unique calcium-binding site. Protein Sci 5, 827-833 PubMed link

Sun, Q., Kuty, G.F., Arockiasamy, A., Xu, M., Young, R., Sacchettini, J.C. 2009. Regulation of a muralytic enzyme by dynamic membrane topology. Nat Struct Mol Biol 11, 1192-1194 PubMed link

Xu, M., Arulandu, A., Struck, D.K., Swanson, S., Sacchettini, J.C., Young, R. 2005. Disulfide isomerization after membrane release of its SAR domain activates P1 lysozyme. Science 307, 113-117 PubMed link