8T0D

Crystal structure of integrin beta-2 tail bound to the FERM-folded talin head domain with E269A/Y270A/K306Q triple mutation

Summary for 8T0D

• Entry DOI: 10.2210/pdb8t0d/pdb
• Related: 8FSE 8FTB 8T0A
• Descriptor: Integrin beta-2,Talin-1 (2 entities in total)
• Functional Keywords: talin, integrin, beta-2, cell adhesion
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 1
• Total formula weight: 47255.29

Authors

Wu, J.,Gao, T. (deposition date: 2023-05-31, release date: 2024-07-03, Last modification date: 2025-05-14)

Primary citation

Gao, T.,Maskalenko, N.A.,Kabir, S.,Campbell, K.S.,Wu, J.
Molecular basis of beta 2 integrin activation by talin unveils subunit-specific mechanisms of integrin signaling.
Cell Rep, 44:115607-115607, 2025

PubMed Abstract: Integrins consist of 24 species, each with unique tissue expression profiles and distinct biological functions. The β subunit of integrin interacts with the FERM-folded head domain of talin through an NPxY/F motif, triggering integrin activation. Although this motif is conserved across most integrin-β subunits, the precise molecular mechanism governing talin's selective recognition of different integrin-β subunits remains unclear. We identify two distinct configurations of the talin head when interacting with β2 and β3 integrins, providing critical insights into subunit-specific recognition of integrins. Structural studies reveal that mutations at the subdomain interface of the talin head can shift its β2-bound configuration to a β3-bound configuration. This shift enhances β2-integrin affinity, leading to increased lymphocyte function-associated antigen-1 (LFA-1)-mediated natural killer cell activity. Together, our data elucidate the structural basis of talin's role in mediating integrin activation in a subunit-specific manner and advance our understanding of how talin may regulate diverse functions of various integrin species.

PubMed: 40310722
DOI: 10.1016/j.celrep.2025.115607

Experimental method

X-RAY DIFFRACTION (2.77 Å)