ORCID Profile
0000-0002-4883-3031
Current Organisation
Lehigh University
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Publisher: Proceedings of the National Academy of Sciences
Date: 26-06-2017
Abstract: Many activating immunoreceptors associate, via interactions between transmembrane domains, with adaptor molecules that mediate signaling for leukocyte activation. To date, the best characterized form of receptor complex assembly depends on a single basic transmembrane (TM) domain residue. We now describe a second, completely different solution for TM-mediated receptor assembly, found in three different Fc receptor TM domains, and involving a more complex polar/aromatic interface. Residues in the core of this interaction motif can also regulate receptor protein turnover. Thus, multiple solutions for TM-mediated receptor assembly with signaling modules have evolved. These findings may provide more broadly useful insights into how other immune receptors that do not contain charged residues in their TM domains assemble into complexes with signaling adaptor molecules.
Publisher: Proceedings of the National Academy of Sciences
Date: 21-11-2022
Abstract: The B cell and T cell antigen receptors (BCR and TCR) share a common architecture in which variable dimeric antigen-binding modules assemble with invariant dimeric signaling modules to form functional receptor complexes. In the TCR, a highly conserved T cell receptor αβ (TCRαβ) transmembrane (TM) interface forms a rigid structure around which its three dimeric signaling modules assemble through well-characterized polar interactions. Noting that the key features stabilizing this TCRαβ TM interface also appear with high evolutionary conservation in the TM sequences of the membrane immunoglobulin (mIg) heavy chains that form the BCR’s homodimeric antigen-binding module, we asked whether the BCR contained an analogous TM structure. Using an unbiased biochemical and computational modeling approach, we found that the mouse IgM BCR forms a core TM structure that is remarkably similar to that of the TCR. This structure is reinforced by a network of interhelical hydrogen bonds, and our model is nearly identical to the arrangement observed in the just-released cryo-electron microscopy (cryo-EM) structures of intact human BCRs. Our biochemical analysis shows that the integrity of this TM structure is vital for stable assembly with the BCR signaling module CD79AB in the B cell endoplasmic reticulum, and molecular dynamics simulations indicate that BCRs of all five isotypes can form comparable structures. These results demonstrate that, despite their many differences in composition, complexity, and ligand type, TCRs and BCRs rely on a common core TM structure that has been shaped by evolution for optimal receptor assembly and stability in the cell membrane.
Publisher: Elsevier BV
Date: 05-2015
Publisher: Proceedings of the National Academy of Sciences
Date: 10-10-2016
Abstract: The T-cell antigen receptor (TCR) is an eight-subunit modular biosensor that detects the presence of pathogen-derived molecular fragments in infected cells and tissues. No atomic-resolution structure has been determined for the intact receptor complex, and the mechanism by which it transmits signals across the cell membrane remains poorly defined. Using a combination of biochemical, biophysical, and computational approaches to study the assembled complex in cellular membranes, we identified an evolutionarily conserved core transmembrane (TM) structure that organizes the complex into an intimately packed eight-helix bundle within the membrane and is critical for the structural integrity of the intact receptor. Our model provides insights into possible structural pathways involved in TM TCR signaling.
Publisher: American Chemical Society (ACS)
Date: 08-10-2020
Publisher: Springer Science and Business Media LLC
Date: 28-04-2022
Publisher: Elsevier BV
Date: 03-2018
No related grants have been discovered for Soohyung Park.