Zhang Heng, Zhu Daniel S, Zhu Jieqing
Versiti Blood Research Institute, Milwaukee, WI, USA.
Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA.
Comput Struct Biotechnol J. 2023 Sep 18;21:4497-4507. doi: 10.1016/j.csbj.2023.09.022. eCollection 2023.
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.
使用以高效和准确著称的AlphaFold2进行蛋白质结构预测的最新进展，为全面分析单个蛋白质家族内的所有结构开辟了新途径。在本研究中，我们评估了AlphaFold2分析整合素结构的能力。整合素是由18种α亚基和8种β亚基组合而成的异二聚体细胞表面受体，形成一个由24个不同成员组成的家族。α和β亚基均由一个大的细胞外结构域、一个短的跨膜结构域以及通常一个短的细胞质尾巴组成。整合素通过识别多种配体在广泛的细胞功能中发挥关键作用。尽管近几十年来整合素结构研究取得了重大进展，但仅确定了有限子集的整合素成员的高分辨率结构，从而限制了我们对整个整合素家族的理解。在此，我们首先在AlphaFold2蛋白质结构数据库中分析了18种α整合素和8种β整合素的单链结构。然后，我们使用新开发的AlphaFold2-多聚体程序预测了所有24种人类整合素的α/β异二聚体结构。预测的结构对α和β亚基的亚结构域显示出高度的准确性，为所有整合素异二聚体提供了高分辨率的结构见解。我们对整个整合素家族的全面结构分析揭示了24个成员之间可能存在的多种构象，为与整合素结构和功能相关的研究提供了一个有价值的结构数据库。我们进一步讨论了源自AlphaFold2的整合素结构的潜在应用和局限性。
