Sundell, G. N. | Search bioRxiv

bioRxiv2026

CHAIR an antigen-resolved antibody-reactome resource for healthy adult immune aging

Antigen-recognition histories accumulate across adult life, but existing human aging resources largely emphasize host-state measurements rather than antigen-resolved humoral memory. We present CHAIR, the Chinese Healthy Aging Immune Resource, which integrates self-antigen, human virome and toxin/virulence-factor PhIP-seq with routine clinical measurements and T/B/NK phenotyping in clinically screened adults aged 20-94 years. The resource framework includes 1,008 unique PhIP-seq samples, 995 clinical records, 977 T/B/NK records and 853 participants with all three layers. Across modeled spaces comprising 23,584 self-antigen targets, 210 virome targets and 1,258 virulence-factor source targets, most measured antibody-reactivity architecture was consistent with broad preservation within domains, whereas age- and sex-associated signals were concentrated in focal targets and modules. Together, CHAIR provides a traceable, antigen-resolved reference framework based on clinically screened adults for investigating focal humoral remodeling across healthy adult aging.

immunology↗

bioRxiv2017

Proteome-wide analysis of phospho-regulated PDZ domain interactions through phosphomimetic proteomic peptide phage display

We report phosphomimetic proteomic peptide-phage display, a powerful large-scale method for finding ligands of short linear motif binding domains that simultaneously pinpoint functional Ser/Thr phosphosites in three steps. First, we computationally designed an oligonucleotide library encoding all human C-terminal peptides containing known or predicted Ser/Thr phosphosites and phosphomimetic variants thereof. Second, we incorporated these oligonucleotides into a phage library. Third, we screened the six PDZ (PSD-95/Dlg/ZO-1) domains of Scribble and DLG1 for binding and identified known and novel ligands from the human proteome, and whether these interactions may be regulated by ligand phosphorylation. We demonstrate that the Scribble PDZ domains preferentially bind to ligands with phosphomimetic mutations at two distinct positions, and show that the equilibrium dissociation constant for Scribble PDZ1 with the C-terminal peptide of RPS6KA2 is enhanced over four-fold by phosphorylation. We elucidate the molecular determinants of phosphopeptide binding through NMR structure determination and mutational analysis. Finally, we discuss the role of Ser/Thr phosphorylation as a switching mechanism of PDZ domain interactions.

biochemistry↗