8VSE

Cryo-EM structure of human CD45 extracellular region in complex with adenoviral protein E3/49K

Summary for 8VSE

• Entry DOI: 10.2210/pdb8vse/pdb
• EMDB information: 43497
• Descriptor: Receptor-type tyrosine-protein phosphatase C, 45.5kDa protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: complex, t cell signaling, viral suppression, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 165075.60

Authors

Borowska, M.T.,Caveney, N.A.,Jude, K.M.,Garcia, K.C. (deposition date: 2024-01-23, release date: 2024-11-06, Last modification date: 2024-11-27)

Primary citation

Borowska, M.T.,Liu, L.D.,Caveney, N.A.,Jude, K.M.,Kim, W.J.,Masubuchi, T.,Hui, E.,Majzner, R.G.,Garcia, K.C.
Orientation-dependent CD45 inhibition with viral and engineered ligands.
Sci Immunol, 9:eadp0707-eadp0707, 2024

PubMed Abstract: CD45 is a cell surface phosphatase that shapes the T cell receptor signaling threshold but does not have a known ligand. A family of adenovirus proteins, including E3/49K, exploits CD45 to evade immunity by binding to the extracellular domain of CD45, resulting in the suppression of T cell signaling. We determined the cryo-EM structure of this complex and found that the E3/49K protein is composed of three immunoglobulin domains assembled as "beads on a string" that compel CD45 into a closely abutted dimer by cross-linking the CD45 D3 domain, leading to steric inhibition of its intracellular phosphatase activity. Inspired by the E3/49K mechanism, we engineered CD45 surrogate ligands that can fine-tune T cell activation by dimerizing CD45 into different orientations and proximities. The adenovirus E3/49K protein has taught us that, despite a lack of a known ligand, CD45 activity can be modulated by extracellular dimerizing ligands that perturb its phosphatase activity and alter T cell responses.

PubMed: 39454026
DOI: 10.1126/sciimmunol.adp0707

Experimental method

ELECTRON MICROSCOPY (3.8 Å)