7E5M

crystal structure of trans assembled human TROP-2

Summary for 7E5M

• Entry DOI: 10.2210/pdb7e5m/pdb
• Descriptor: Tumor-associated calcium signal transducer 2, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: trop-2, crystal, sacituzumab, assembly, tumor, cell adhesion
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 53600.95

Authors

Sun, M.,Zhang, H.,Chai, Y.,Qi, J.,Gao, G.F.,Tan, S. (deposition date: 2021-02-19, release date: 2021-12-15, Last modification date: 2024-10-09)

Primary citation

Sun, M.,Zhang, H.,Jiang, M.,Chai, Y.,Qi, J.,Gao, G.F.,Tan, S.
Structural insights into the cis and trans assembly of human trophoblast cell surface antigen 2.
Iscience, 24:103190-103190, 2021

PubMed Abstract: Human trophoblast cell surface antigen 2 (TROP-2) is an important target of tumor therapy, and antibody-drug conjugates with sacituzumab targeting TROP-2 have been approved for the treatment of triple-negative breast cancer. Here, we report the crystal structures of TROP-2-ECD, which can be either or dimers depending on which distinct but overlapping interfaces is used to engage with monomers. The or -tetrameric forms of TROP-2 can also be assembled with a non-overlapping interface with either - or dimerization, suggesting that - and dimers cluster on the cell surface. The binding site of sacituzumab on TROP-2 is mapped to be located on a stretched polypeptide in CPD (Q237-Q252), which is not involved in either or interactions. The present findings will improve understanding of the molecular assembly of TROP-2 on tumor cells and shed light on future design of biologics for tumor therapy.

PubMed: 34693228
DOI: 10.1016/j.isci.2021.103190

Experimental method

X-RAY DIFFRACTION (3.2 Å)