8VOI

HADDOCK models of active human alphaM I-domain bound to the the C-terminal domain of the cytokine pleiotrophin

Summary for 8VOI

• Entry DOI: 10.2210/pdb8voi/pdb
• NMR Information: BMRB: 31139
• Descriptor: Integrin alpha-M, Pleiotrophin, MAGNESIUM ION (3 entities in total)
• Functional Keywords: integrin, mac-1, pleiotrophin, cell adhesion
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 27644.95

Authors

Wang, X.,Nguyen, H. (deposition date: 2024-01-15, release date: 2024-05-15, Last modification date: 2025-05-28)

Primary citation

Nguyen, H.,Podolnikova, N.P.,Ugarova, T.P.,Wang, X.
alpha M I-domain of integrin Mac-1 binds the cytokine pleiotrophin using multiple mechanisms.
Structure, 32:1184-1196.e4, 2024

PubMed Abstract: The integrin Mac-1 (αβ, CD11b/CD18, CR3) is an adhesion receptor expressed on macrophages and neutrophils. Mac-1 is also a promiscuous integrin that binds a diverse set of ligands through its αI-domain. However, the binding mechanism of most ligands remains unclear. We have characterized the interaction of αI-domain with the cytokine pleiotrophin (PTN), a protein known to bind αI-domain and induce Mac-1-mediated cell adhesion and migration. Our data show that PTN's N-terminal domain binds a unique site near the N- and C-termini of the αI-domain using a metal-independent mechanism. However, a stronger interaction is achieved when an acidic amino acid in a zwitterionic motif in PTN's C-terminal domain chelates the divalent cation in the metal ion-dependent adhesion site of active αI-domain. These results indicate that αI-domain can bind ligands using multiple mechanisms and that the active αI-domain has a preference for motifs containing both positively and negatively charged amino acids.

PubMed: 38729161
DOI: 10.1016/j.str.2024.04.013

Experimental method

SOLUTION NMR