An enigmatic protein finally reveals its structure: Themis wraps around Grb2 in a surprising embrace.
Key Details
- Researchers at VIB, Ghent University, and VUB have determined the three-dimensional structure of the Themis protein bound to Grb2.
- The findings were published in Nature Communications on 27 May 2026.
- The study used cryo-electron microscopy to reveal that Themis wraps around Grb2 in a previously unknown intricate manner, with part of Grb2 remaining flexible.
Background
T cells undergo selection in the thymus before becoming functional. Dysregulation of this process can contribute to autoimmune diseases or immune deficiencies. Themis has been known for nearly two decades to be essential for this developmental checkpoint, but its molecular mechanism was unclear.
Findings
The interaction between Themis and Grb2 involves multiple cooperative contact points that stabilize a constitutive complex. Disrupting this interaction interferes with signaling events essential for proper T cell development.
Statements
"Themis has always been something of an enigma. We knew it played a critical role in T cell development, but we lacked a structural understanding of how it interacts with signaling partners."
— Dr. Danielle Clancy (VIB-UGent)
"What surprised us most was how extensively Themis embraces Grb2."
— Prof. Savvas Savvides (VIB-UGent)