Chauhan Shilpa, Thakur Ankit, Kulharia Mahesh, Verma Shailender Kumar
Centre for Computational Biology and Bioinformatics, Central University of Himachal Pradesh, Kangra, 176206, India.
Department of Environmental Studies, University of Delhi, New Delhi, Delhi, 110007, India.
Protein J. 2025 Apr 29. doi: 10.1007/s10930-025-10266-9.
In cancer biology, copper-binding proteins (CBPs) possess a wide range of roles that impact various aspects of tumour development and progression. Modifications in CBPs in malignancy may have an enormous effect on cellular processes essential for the development and growth of cancers. We utilised bioinformatics approaches to separate down CBPs in the cancer proteome, and 32 proteins have been determined to be putative CBPs. Twelve of these proteins were associated with a likelihood of metastatic spread from primary to secondary cancer regions. Results indicated that the point mutation causes structural and functional changes in the proteins. Point mutations also alter the Cu binding sites and drug molecules' binding affinity for CBPs. The majority of mutations disrupt copper binding sites in CBPs, based on subsequent mutation studies focused on proteins P61769:B2MG (Beta-2-microglobulin) and P42684:ABL2 (Tyrosine kinase protein ABL2) due to their high and low expression profile respectively, in various cancer types. The copper ion binding sites and drug-binding affinity for B2MG and ABL2 highlighted in the case study represent the impact of point mutation on the proteins. This study highlighted the possible effect of mutations in CBPs, representing that the point mutations disrupt the intramolecular interactions of the proteins and simultaneously alter the other molecules' binding affinity.
在癌症生物学中，铜结合蛋白（CBPs）具有广泛作用，影响肿瘤发生和发展的各个方面。恶性肿瘤中CBPs的修饰可能对癌症发生和生长所必需的细胞过程产生巨大影响。我们利用生物信息学方法在癌症蛋白质组中筛选出CBPs，已确定32种蛋白质为假定的CBPs。其中12种蛋白质与原发性癌症区域转移至继发性癌症区域的可能性相关。结果表明，点突变导致蛋白质的结构和功能发生变化。点突变还会改变铜结合位点以及药物分子与CBPs的结合亲和力。基于后续针对蛋白质P61769:B2MG（β-2-微球蛋白）和P42684:ABL2（酪氨酸激酶蛋白ABL2）的突变研究，由于它们在各种癌症类型中分别具有高表达和低表达特征，大多数突变破坏了CBPs中的铜结合位点。案例研究中突出显示的B2MG和ABL2的铜离子结合位点及药物结合亲和力代表了点突变对蛋白质的影响。这项研究突出了CBPs中突变的可能影响，表明点突变破坏了蛋白质的分子内相互作用，同时改变了其他分子的结合亲和力。
