Biology subjects

Dichiara-Rodriguez, M. G.

Publications and source records attributed to Dichiara-Rodriguez, M. G..

3 recordsLinked to original sources

bioRxiv2026

Structural presentation of amyloid β by HLA

HLA-DR-restricted T-cell reactivity to amyloid {beta} (A{beta}) has been associated with Alzheimers disease (AD), but structural evidence for HLA presentation of A{beta}-derived peptides remains elusive. We present the crystal structure of the A{beta}1-15 fragment bound to HLA-DR1, providing, to the best of our knowledge, the first experimental structure of an Alzheimers A{beta} peptide bound to an HLA molecule. The molecular architecture of this complex defines a peptide:MHC interaction dictated by engagement of A{beta}1-15 peptide central core with further involvement of N- and C-terminal peptide flanks. The structure reveals that DR{beta}1 Arg70, a polymorphic position, directly binds P4 and P5 through polar contacts, providing a rationale for HLA-DRB allelic bias underpinning accommodation of A{beta}1-15. We also describe the A{beta}1-15:HLA-DRB1 surface topology, informing a candidate binding surface for potential T-cell recognition. Collectively, these findings contribute a structural framework for further research in the context of A{beta}-specific CD4+ T-cell autoreactivity in AD.

neuroscience↗

bioRxiv2025

Structure of Factor VII Gla domain bound to EPCR

The precise molecular determinants that underlie the binding of activated factor VII (FVIIa) to the endothelial cell protein C receptor (EPCR) have long remained unresolved. We report here the crystal structure of factor VII Gla domain bound to human EPCR, revealing a binding geometry in essence indistinguishable from that of the PC-EPCR interface and confirming absolute structural competition for EPCR binding. Relative to previous FVII structures, we observe receptor-dependent repositioning of the Gla {omega} loop coupled to a selective arrangement in which metal ion at position four adopts a Ca2+-compatible and EPCR-restricted coordination state. These findings resolve a long-standing gap and inform the structural basis for the binding of EPCR to FVIIa, a current therapeutic intervention in hemophilia.

biochemistry↗

bioRxiv2025

Robust TCR production for the structural study of TCR-pMHC complexes

A precise comprehension of how T cell receptors (TCRs) engage their antigens is pivotal for advancing basic research and T cell immunotherapy in cancer. While TCR refolding from inclusion bodies has greatly facilitated X-ray studies over the past decades, the procedures remain labor-intensive and can yield poorly. We have developed a simplified strategy for efficient production of soluble TCRs in CHO cells which, coupled with the removal of N-glycosylation, enable structural studies of TCR-pMHC complexes. An equivalent of just 20 ml of cell culture delivered sufficient deglycosylated TCR (dgTCR) to screen, upon complexation with a cognate pMHC, over 350 crystallization conditions and obtain a high-resolution dataset. This approach illustrates an effective alternative for TCR production to support studies devoted to research and development of TCRs.

immunology↗