The actual molecular handshakes happening inside a human brain can now be seen, revealing a specific protein pairing linked to suicide and depression.
Most of what we know about brain receptors comes from studying artificial cells in a petri dish. A new technique uses nanobodies to pull actual protein complexes directly out of preserved human brain tissue. Researchers discovered that two specific receptors, mGluR2 and mGluR3, often stick together in the brains of people who died by suicide. This exact pairing is much rarer in healthy brains, suggesting it plays a role in severe mental illness. Mapping these native protein assemblies opens a new door to creating drugs that target the specific social life of brain proteins.
Molecular Dissection of Protein Complexes Isolated from Sections of Human Brain
SSRN · 6719146
Molecular studies of brain receptors and transporters have typically relied on recombinant systems, limiting insight into their organization in native tissue. Here, we develop nanobody-based immunoprecipitation coupled with native mass spectrometry to interrogate endogenous protein assemblies from post-mortem mouse and human brain sections. We exemplify our approach by characterizing the synaptic proteins VGluT1 and mGluR2. From a single mouse brain, we discover mGluR2/3 heterodimers, alongside