2N4I

The solution structure of Skint-1, a critical determinant of dendritic epidermal gamma-delta T cell selection

Summary for 2N4I

• Entry DOI: 10.2210/pdb2n4i/pdb
• NMR Information: BMRB: 17833
• Descriptor: Selection and upkeep of intraepithelial T-cells protein 1 (1 entity in total)
• Functional Keywords: immune stress surveillance, thymic organ culture, signaling protein
• Biological source: Mus musculus (mouse)
• Cellular location: Membrane ; Multi-pass membrane protein : A7TZE6
• Total number of polymer chains: 1
• Total formula weight: 13569.28

Authors

Salim, M.,Knowles, T.J.,Hart, R.,Mohammed, F.,Woodward, M.J.,Willcox, C.R.,Overduin, M.,Hayday, A.C.,Willcox, B.E. (deposition date: 2015-06-18, release date: 2016-03-02, Last modification date: 2024-10-09)

Primary citation

Salim, M.,Knowles, T.J.,Hart, R.,Mohammed, F.,Woodward, M.J.,Willcox, C.R.,Overduin, M.,Hayday, A.C.,Willcox, B.E.
Characterization of a Putative Receptor Binding Surface on Skint-1, a Critical Determinant of Dendritic Epidermal T Cell Selection.
J.Biol.Chem., 291:9310-9321, 2016

PubMed Abstract: Dendritic epidermal T cells (DETC) form a skin-resident γδ T cell population that makes key contributions to cutaneous immune stress surveillance, including non-redundant contributions to protection from cutaneous carcinogens. How DETC become uniquely associated with the epidermis was in large part solved by the identification of Skint-1, the prototypic member of a novel B7-related multigene family. Expressed only by thymic epithelial cells and epidermal keratinocytes, Skint-1 drives specifically the development of DETC progenitors, making it the first clear candidate for a selecting ligand for non-MHC/CD1-restricted T cells. However, the molecular mechanisms underpinning Skint-1 activity are unresolved. Here, we provide evidence that DETC selection requires Skint-1 expression on the surface of thymic epithelial cells, and depends upon specific residues on the CDR3-like loop within the membrane-distal variable domain of Skint-1 (Skint-1 DV). Nuclear magnetic resonance of Skint-1 DV revealed a core tertiary structure conserved across the Skint family, but a highly distinct surface charge distribution, possibly explaining its unique function. Crucially, the CDR3-like loop formed an electrostatically distinct surface, featuring key charged and hydrophobic solvent-exposed residues, at the membrane-distal tip of DV. These results provide the first structural insights into the Skint family, identifying a putative receptor binding surface that directly implicates Skint-1 in receptor-ligand interactions crucial for DETC selection.

PubMed: 26917727
DOI: 10.1074/jbc.M116.722066

Experimental method

SOLUTION NMR