Steven L Mcknight
University of Texas Southwestern Medical Center, TX·Biochemistry
Most proteins use all 20 amino acids and fold into stable shapes. Yet 10-20% of proteins in human and other eukaryotic cells contain long stretches built from only a few amino acids.
- Fields
Biochemistry
Biophysics
Neuroscience
- Topics
low complexity domains
intrinsically disordered proteins
phase separation
- Grants
- 1 known grant, through Jan 2029
What they work on
- Identify and map thousands of distinct labile cross-beta cores, the short segments that nucleate self-association, within low-complexity domains across the human proteome using high-throughput methods.
- Resolve how transiently self-associated cross-beta cores selectively recruit other proteins to build dynamic cellular structures, using biochemical, molecular biological and biophysical approaches.
- Relate cross-beta core assembly in proteins such as FUS, TDP-43, hnRNPA2 and ataxin-2 to how phosphorylation, methionine oxidation and disease mutations disassemble or aberrantly stabilize RNA granules and intermediate filaments.
More about the research
These low-complexity (LC) domains were long thought to have no fixed structure. Even so, upwards of 75% of all chemical modifications added to proteins after they are made, and more than half of alternative RNA splicing events, map to LC domains, suggesting a large share of cellular regulation runs through them. This research asks how LC domains stick to themselves and to partner proteins to build dynamic structures inside cells, and how this goes wrong in disease.
Why it matters
Mutations in low-complexity protein domains can wrongly stabilize assemblies that should be short-lived, a route to neurological and neurodegenerative disease. A proteome-wide map of cross-beta cores, plus an account of how they recruit partner proteins, could help explain how such mutations cause disease and which proteins and regions are most vulnerable.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Lin Guo
Thomas Jefferson University, PA·Biochemistry
Determine how the nuclear import receptor Kapβ2 engages and chaperones newly found partner proteins that lack a nuclear localization signal, using cryo-electron microscopy to solve their structures.
Daniel Dominguez
University of North Carolina at Chapel Hill, NC·Biochemistry
Define the mechanisms by which intrinsically disordered low-complexity domains (LCDs) of RNA binding proteins recognize structured RNA, such as RNA G-quadruplexes, using biochemical and computational approaches.
Priya R. Banerjee
University at Buffalo, NY·Biophysics·Early-career
Test whether pioneer transcription factors, proteins that can bind DNA packed into closed chromatin, act by forming liquid-like droplets on DNA that concentrate RNA polymerases and nucleosome-remodeling complexes to switch genes on.
The school
University of Texas Southwestern Medical Center: 40 labs on PI Pages, $869M a year on research, 86 research doctorates a year.
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