A heterodimeric receptor subunit, Integrin αV, often complexed with Integrin β3 plays a vital role in cell signaling to regulate angiogenesis and promote cancer progression. The paramount β-turn formed from pentapeptide residues (PPQEE) in the cytoplasmic domain of Integrin αV was previously reported as crucial for cell signaling and its deletion was proved deleterious for protein's cell membrane adhesion and ligand binding properties. This study revealed conformational changes in the Integrin αV subunit upon deletion of PPQEE residues through in silico structural modelling approach followed by analysis of alteration of binding sites. Human Protein Atlas database helped to identify the association of Integrin αV to the unfavourable prognosis of three gastrointestinal cancers: stomach, liver and pancreatic cancers. Molecular modelling and docking techniques were carried out for the necessary complex formations (wild-type and mutant-type). Further comparison was performed for the complexes. The changes in protein's conformation and stability due to PPQEE deletion were observed in both independent subunit and heterodimer. The most noteworthy conformational shift was the disruption of a transmembrane helix into coil, which accounted for protein's impaired cell membrane adhesion, increased solvent accessibility and decreased stability. The deletion also caused a reduction of beta-turn regions, which disrupted ligand binding in the cytoplasmic domain of Integrin αV subunit. This study emphasized on structural basis of how the deletion of PPQEE residues alters stability, ligand binding and signaling activity of Integrin αV subunit highlighting the importance of these residues in maintenance of protein's native structure.

异二聚体受体亚基 Integrin αV 通常与 Integrin β3 复合，在调节血管生成和促进癌症进展的细胞信号传导中起着至关重要的作用。由整合素 αV 细胞质域中的五肽残基 (PPQEE) 形成的最重要的 β-转角先前被报道为对细胞信号传导至关重要，并且其缺失被证明对蛋白质的细胞膜粘附和配体结合特性有害。该研究揭示了通过计算机模拟删除 PPQEE 残基后整联蛋白 αV 亚基的构象变化结构建模方法，然后分析结合位点的改变。人类蛋白质图谱数据库帮助确定了整合素 αV 与三种胃肠道癌症：胃癌、肝癌和胰腺癌的不良预后的关联。对必要的复杂地层（野生型和突变型）进行了分子建模和对接技术。对复合物进行了进一步比较。在独立亚基和异二聚体中均观察到由于 PPQEE 缺失导致蛋白质构象和稳定性的变化。最值得注意的构象变化是跨膜螺旋被破坏成卷曲，这解释了蛋白质细胞膜粘附受损、溶剂可及性增加和稳定性降低。删除还导致β转角区域减少，这破坏了整合素αV亚基细胞质域中的配体结合。该研究强调了 PPQEE 残基的缺失如何改变整联蛋白 αV 亚基的稳定性、配体结合和信号传导活性的结构基础，突出了这些残基在维持蛋白质天然结构中的重要性。