Deciphering Membrane Protein Structures Through Scattering and Modeling: Insights Into TSPO, a Neuroimaging Key Marker

by Sophie Combet (Laboratoire Léon-Brillouin (LLB))

Monday Dec 9, 2024, 2:30 PM → 3:30 PM Europe/Berlin

PH HS 3 (Physics Department)

Despite remarkable advances in artificial intelligence, including transformative tools like AlphaFold, predicting the structures of membrane protein remains a major challenge in structural biology. These proteins account for 30% of the proteome and 60% of therapeutic targets, yet they are notably underrepresented in the Protein Data Bank (PDB), with only 3% of resolved structures. This disparity arises from the difficulty of preserving their native state in amphiphilic environments, which complicates their study using classical structural techniques (X-ray crystallography, NMR, cryo-EM).

In this context, combining small-angle X-ray and neutron scattering (SAXS/SANS) with computational modeling offers a powerful alternative. This approach, while providing low-resolution structural data, enables investigations under near-physiological conditions.

I will illustrate this methodology using TSPO, a transmembrane protein that serves as a key neuroimaging marker in cancers and neurodegenerative diseases [1, 2].

References:
1. Combet, S. et al. Effect of amphiphilic environment on the solution structure of mouse TSPO translocator protein. Biochimie 205, 61–72 (2023). doi.org/10.1016/j.biochi.2022.11.014
2. Saade, C. et al. Enhanced structure/function of mTSPO translocator in lipid: surfactant mixed micelles. Biochimie 224, 3–15 (2024). doi.org/10.1016/j.biochi.2024.04.008