Family-wide analysis of integrin structures predicted by AlphaFold2

Abstract

Recent advances in protein structure prediction using AlphaFold2, known for its high efficiency and accuracy, have opened new avenues for comprehensive analysis of all structures within a single protein family. In this study, we evaluated the capabilities of AphaFold2 in analyzing integrin structures. Integrins are heterodimeric cell surface receptors composed of a combination of 18 α and 8 β subunits, resulting in a family of 24 different members. Both α and β subunits consist of a large extracellular domain, a short transmembrane domain, and typically, a short cytoplasmic tail. Integrins play a pivotal role in a wide range of cellular functions by recognizing diverse ligands. Despite significant advances in integrin structural studies in recent decades, high-resolution structures have only been determined for a limited subsets of integrin members, thus limiting our understanding of the entire integrin family. Here, we first analyzed the single-chain structures of 18 α and 8 β integrins in the AlphaFold2 protein structure database. We then employed the newly developed AlphaFold2-multimer program to predict the α/β heterodimer structures of all 24 human integrins. The predicted structures show a high level of accuracy for the subdomains of both α and β subunits, offering high-resolution structure insights for all integrin heterodimers. Our comprehensive structural analysis of the entire integrin family unveils a potentially diverse range of conformations among the 24 members, providing a valuable structure database for studies related to integrin structure and function. We further discussed the potential applications and limitations of the AlphaFold2-derived integrin structures.