C4BPA

Background

Complement C4 binding protein alpha chain (C4BPA) is an important component of the C4BP complex. Usually, human C4BPA is composed of six/seven identical α chains, each α chain consists of 8 complement control protein (CCP) repeat domains. By comparison, mouse C4BPA consists of 7 α chains and each α chain contains 6 CCP domains. There are two cysteine residues and an amphipathic a-helix at the C-terminal of each α chain, which is responsible for intracellular polymerization of the C4BP complex. On the α chain lie different binding sites of various ligands.

Human C4BPA is a 67 kDa protein with 597 amino acids. The CCP1-3 domain of the α chain is the binding site of activated complement C4b. When the C4BPA binds to the cell-bound C4d fragment, the C4b will be cleaved by the complement factor I, a serine protease that regulates complement activation. Thus, C4BPA serves as a cofactor of factor I or a negative regulator, inactivating the C4b into C4c and C4d, thereby inhibiting the over activation of the complement classical pathway and complement lectin pathway. The abnormality of C4BPA is likely to cause the over-activation or dysfunction of the complement system, causing disorders like acute poststreptococcal glomerulonephritis and protein S deficiency.

Fig.1 C4BP structure.^{1, 3}

C4BPA Functional Service

Creative Biolabs provides a wide spectrum of C4BPA-focused products, including anti-C4BPA antibodies, ELISA kits, recombinant C4BPA proteins, and vectors containing C4BPA clones. These tools are expertly crafted to enable the identification and analysis of interactions between complement factors and C4BPA proteins. They play a pivotal role in advancing research aimed at developing therapeutic strategies for an array of diseases.

Fig.2 Immunohistochemical profiling of C4BPA, CD40, and CD8 in excised human pancreatic ductal adenocarcinoma specimens.^{2, 3}

Scientists have recognized C4BPA as a serum biomarker pivotal for the early diagnosis of pancreatic ductal adenocarcinoma (PDAC) and have investigated its functional significance within PDAC cells and the surrounding tumor microenvironment. Using immunohistochemical staining, researchers assessed stromal C4BPA, its associated binding partner CD40, and the abundance of CD8⁺ tumor-infiltrating lymphocytes within resected human PDAC tissues. Their findings showed that elevated stromal C4BPA and CD40 correlated with a positive PDAC prognosis and a higher count of CD8⁺ lymphocytes. Experiments further demonstrated that recombinant human C4BPA augmented the numbers of CD4⁺ and CD8⁺ T cells in PBMCs, promoted the proliferation of PDAC cells expressing CD40, and elevated both murine T lymphocytes and CD8⁺ tumor-infiltrating lymphocytes, observed in vitro and in vivo.

Creative Biolabs provides a wide-ranging suite of functional services focusing on C4BPA, encompassing comprehensive interaction studies and diverse specialized evaluations. These expertly tailored services are designed to aid our clients in advancing their scientific investigations and clinical projects.