The integrin Mac-1 (α_Mβ₂, 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 α_MI-domain. However, the binding mechanism of most ligands remains unclear. We have characterized the interaction of α_MI-domain with the cytokine pleiotrophin (PTN), a protein known to bind α_MI-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 α_MI-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 α_MI-domain. These results indicate that α_MI-domain can bind ligands using multiple mechanisms and that the active α_MI-domain has a preference for motifs containing both positively and negatively charged amino acids.

整合素 Mac-1 (α _M β ₂、CD11b/CD18、CR3) 是巨噬细胞和中性粒细胞上表达的粘附受体。 Mac-1 也是一种混杂的整合素，通过其 α _M I 结构域结合多种配体。然而，大多数配体的结合机制仍不清楚。我们已经表征了 α _M I 结构域与细胞因子多效蛋白 (PTN)的相互作用，PTN 是一种已知结合 α _M I 结构域并诱导 Mac-1 介导的细胞粘附和迁移的蛋白质。我们的数据表明，PTN 的 N 端结构域使用金属独立机制结合 α _M I 结构域N 端和 C 端附近的独特位点。然而，当 PTN 的 C 端结构域中的两性离子基序中的酸性氨基酸螯合活性 α _M I 结构域的金属离子依赖性粘附位点中的二价阳离子时，会实现更强的相互作用。这些结果表明α _M I-结构域可以使用多种机制结合配体，并且活性α _M I-结构域偏爱包含带正电荷和带负电荷的氨基酸的基序。