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bioRxiv · 10.1101/2023.05.02.539023

Family-wide analysis of integrin structures predicted by AlphaFold2

Zhang, H.·Zhu, D. S.·Zhu, J.
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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 and 8 {beta} subunits, resulting in a family of 24 different members. Both and {beta} 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 and 8 {beta} integrins in the AlphaFold2 protein structure database. We then employed the newly developed AlphaFold2-multimer program to predict the /{beta} heterodimer structures of all 24 human integrins. The predicted structures show a high level of accuracy for the subdomains of both and {beta} 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.

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Zhang, H., Zhu, D. S., Zhu, J.. 2023-05-02. Family-wide analysis of integrin structures predicted by AlphaFold2. https://doi.org/10.1101/2023.05.02.539023

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