Life Sciences & Biotechnology
Title : | Towards designing tunable nano-machines: Taking advantage of protein disorder |
Area of research : | Life Sciences & Biotechnology, Medical Sciences |
Focus area : | Protein biophysics |
Principal Investigator : | Dr. Athi Narayanan Naganathan, Assistant Professor, Indian Institute of Technology (IIT), Madras |
Timeline Start Year : | 2015 |
Timeline End Year : | 2020 |
Contact info : | athi@iitm.ac.in |
Details
Executive Summary : | How are evolutionary selected functional and conformational features
imprinted on the sequence, and how does Nature introduce multi-functionality
into proteins through minimal changes in primary sequence? Is functional
promiscuity compromised in going from a disordered domain to a well-folded
structure? Can a quantitative picture of the interplay between energetic
frustration, folding speed, stability and functional constraints be detailed at
the amino-acid level on homologous proteins? How can these structural energetic subtleties at both local and global level be interwoven to design
protein-based nano-sensors?
We plan to answer these questions by studying homologous proteins that
display extremes of disorder tendency and promiscuity – one completely
unstructured, promiscuous and exhibiting weak DNA-binding (CytR) and the
other well-folded, displaying specific and strong DNA-binding (LacR). CytR
folds upon binding DNA to a structure resembling LacR.We therefore plan to
construct a mutational path from the disordered CytR to the ordered LacR
through rational protein design, extensive ensemble spectroscopic
characterization, and DNA-binding assays. The connection between
patterning of amino-acids, structure and functional promiscuity gleaned from
this approach would then be exploited (together with a simple model) to
design protein-based versatile sensors that can rapidly detect minor changes
in ambient conditions and report them via reliable spectral signatures. |
Total Budget (INR): | 3,37,53,676 |
Achievements : | 1) Identified the origins of disorder in an intrinsically disordered protein
2) Engineered order from disorder
3) Salt-sensitivity of DNA-binding proteins explained
4) A novel method to quantify binding isotherms with a simplistic model
5) Origins of collapse transition in a disordered protein and the associated binding heterogeneity
6) First report of excited folded-like conformation in a disordered ensemble
7) First accurate measurement of absolute heat capacity of IDPs |
Publications : | 9 |
PhD Produced : | 2 |
Innovation (Innovations/ Patents/ Tech Transfer) : | Using multi-probe and multi-model approaches to probe and understand the conformational behavior of proteins. |
Outcome/Output: | Identified organizational principles behind sensing of salt by proteins which can be incorporated into other systems |
Organizations involved