9BNC

Collagen XVIII trimerization domain with introduced inter-chain disulfide bond, E31C-V37C

Summary for 9BNC

• Entry DOI: 10.2210/pdb9bnc/pdb
• Descriptor: Collagen alpha-1(XVIII) chain, SULFATE ION, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• Functional Keywords: trimer, disulfide, biologic scaffold, structural protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 3
• Total formula weight: 19634.57

Authors

Young, T. (deposition date: 2024-05-02, release date: 2025-08-27, Last modification date: 2025-10-29)

Primary citation

Gonzales, J.,Young, T.,Choi, H.,Park, M.,Jewel, Y.,Fan, C.,Purohit, R.,Bjorkman, P.J.,Williams, J.C.
Development of an ultrahigh affinity, trimeric ACE2 biologic as a universal SARS-CoV-2 antagonist.
Commun Biol, 8:1428-1428, 2025

PubMed Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, utilizes membrane-bound, angiotensin-converting enzyme II (ACE2) for internalization and infection. We describe the development of a biologic that takes advantage of the proximity of the N-terminus of bound ACE2 to the three-fold symmetry axis of the spike protein to create an ultrapotent, trivalent ACE2 entry antagonist. Distinct disulfide bonds were added to enhance serum stability and a single point mutation was introduced to eliminate enzymatic activity. Through surface plasmon resonance, pseudovirus neutralization assays, and single-particle cryo-electron microscopy, we show this antagonist binds to and inhibits SARS-CoV-2 variants. We further show the antagonist binds to and inhibits a 2003 SARS-CoV-1 strain. Collectively, structural insight has allowed us to design a universal trivalent antagonist against all variants of SARS-CoV-2 tested, suggesting it will be active against the emergence of future mutants.

PubMed: 41053501
DOI: 10.1038/s42003-025-08819-w

Experimental method

X-RAY DIFFRACTION (1.4 Å)