John Hunt
Columbia University, NY·Biophysics
Proteins are not static sculptures; many of them are machines that move, and the moving is the point. We understand protein shapes far better than protein motions, largely because standard structural methods capture only stable, long-lived states.
- Fields
Biophysics
Biochemistry
Biology
- Topics
ABC transporters
BtuCD-F
vitamin B12 transport
- Grants
- 1 known grant, through Jun 2028
What they work on
- Use single-molecule FRET with vitamin B12 quenching (smFRET-Q) to track individual substrate molecules in real time during ATP-driven transport by the E. coli importer BtuCD-F reconstituted into nanodiscs.
- Apply double mutant-cycle analysis to test how side-chain packing interactions within the transmembrane domains of BtuCD shape the landscape of conformations available during B12 translocation.
- Determine how local electrostatic interactions in the ATPase active site are propagated into directional progression through the transport cycle, testing how hydrolysis of single ATP molecules drives the power stroke.
- Guide mutant selection using protein sequence analysis, including evolutionary correlations between pairs of amino acids, and test whether such sequence methods can predict functionally important dynamics.
More about the research
This project studies motion directly in one family of molecular machines: ATP-Binding Cassette (ABC) transporters, which burn ATP, the cell's energy currency, to pump substrates across membranes. The specific question is how a protein's amino acid sequence encodes the particular motions it needs to do mechanical work.
Why it matters
Most drug design and protein engineering rests on static structures, yet many proteins only work because they move in particular ways. Methods that read out functional motion one molecule at a time, and connect it back to sequence, could support the development of drugs that modulate dynamically active proteins and the engineering of proteins with new molecular activities. ABC transporters themselves are required for bacterial growth and pathogenesis.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
David Cafiso
University of Virginia, VA·Biophysics
Test models of how TonB-dependent transporters such as BtuB, the vitamin B12 transporter, move nutrients across the E. coli outer membrane, using site-directed spin labeling and EPR spectroscopy on active proteins.
Stephanie Gates
University of Missouri-Columbia, MO·Biochemistry
Dissect how the Hsp70/CHIP/BAG-1 chaperone complex affects each step of proteasomal degradation, including ubiquitin tagging, substrate binding and breakdown, using in vitro assays with purified proteins.
Jochen Zimmer
University of Virginia, VA·Biochemistry
Determine how cellulose biosynthesis is controlled in enterobacteria such as E. coli, building on the lab's structures of the supramolecular cellulose synthase complex that both polymerizes and secretes this glucose chain.
The school
Columbia University: 89 labs on PI Pages, $1.4B a year on research, 625 research doctorates a year.
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