The nonpolymorphic class Ib molecule, HLA-E, primarily presents peptides from HLA class Ia leader peptides, providing an inhibitory signal to NK cells via CD94/NKG2 interactions. Although peptides of pathogenic origin can also be presented by HLA-E to T cells, the molecular basis underpinning their role in antigen surveillance is largely unknown. Here, we solved a co-complex crystal structure of a TCR with an HLA-E presented peptide (pHLA-E) from bacterial (Mycobacterium tuberculosis) origin, and the first TCR-pHLA-E complex with a noncanonically presented peptide from viral (HIV) origin. The structures provided a molecular foundation to develop a novel method to introduce cysteine traps using non-natural amino acid chemistry that stabilized pHLA-E complexes while maintaining native interface contacts between the TCRs and different pHLA-E complexes. These pHLA-E monomers could be used to isolate pHLA-E-specific T cells, with obvious utility for studying pHLA-E restricted T cells, and for the identification of putative therapeutic TCRs.
The domesticated silkworm , an essential industrial animal for silk production, has attracted attention as a host for protein production due to its remarkable protein synthesis capability. Here, we applied genetic code expansion (GCE) using a versatile pyrrolysyl-tRNA synthetase (PylRS)/tRNA pair from to ; GCE enables synthetic amino acid incorporation into proteins to give them non-natural functions. Transgenic lines expressing PylRS and its cognate tRNA were generated and cross-mated to obtain their F hybrid.
Objectives: Early-onset schizophrenia (EOS) is a severe and chronic mental disease that manifests during childhood and adolescence. There are currently no objective biomarkers to diagnose this psychosis. Recent research has shown that metabolic disorders are closely associated with the onset of schizophrenia, but there is a lack of evidence among children and adolescent populations.
Antimicrobial peptides (AMPs) are regarded as promising candidates for combating antimicrobial resistance. Previously we identified an AMP named -CATH2 from the green sea turtle, which exhibited potent antibacterial activity and attractive potential in application. However, natural AMPs including -CATH2 frequently suffer from structural instability and sensitivity to physiological conditions, limiting their effectiveness.
Engineered heme proteins exhibit excellent sustainable catalytic carbene transfer reactivities toward olefins for value-added cyclopropanes. However, unactivated and electron-deficient olefins remain challenging in such reactions. To help design efficient heme-inspired biocatalysts for these difficult situations, a systematic quantum chemical mechanistic study was performed to investigate effects of olefin substituents, non-native amino acid axial ligands, and natural and non-natural macrocycles with the widely used ethyl diazoacetate.
Many non-natural amino acids can be incorporated by biological systems into coded functional peptides and proteins. For such incorporations to be effective, they must not only be compatible with the desired function but also evade various biochemical error-checking mechanisms. The underlying molecular mechanisms are complex, and this problem has been approached previously largely by expert perception of isomer compatibility, followed by empirical study.
