6CK8

Crystal structure of anti-influenza single-domain llama antibody SD38

Summary for 6CK8

• Entry DOI: 10.2210/pdb6ck8/pdb
• Descriptor: Llama antibody SD38, SULFATE ION, PENTAETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: single-domain, multi-domain, llama, antibody, influenza, broad, neutralization, immune system
• Biological source: Lama glama
• Total number of polymer chains: 3
• Total formula weight: 43484.50

Authors

Zhu, X.,Wilson, I.A. (deposition date: 2018-02-27, release date: 2018-11-14, Last modification date: 2023-10-04)

Primary citation

Laursen, N.S.,Friesen, R.H.E.,Zhu, X.,Jongeneelen, M.,Blokland, S.,Vermond, J.,van Eijgen, A.,Tang, C.,van Diepen, H.,Obmolova, G.,van der Neut Kolfschoten, M.,Zuijdgeest, D.,Straetemans, R.,Hoffman, R.M.B.,Nieusma, T.,Pallesen, J.,Turner, H.L.,Bernard, S.M.,Ward, A.B.,Luo, J.,Poon, L.L.M.,Tretiakova, A.P.,Wilson, J.M.,Limberis, M.P.,Vogels, R.,Brandenburg, B.,Kolkman, J.A.,Wilson, I.A.
Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin.
Science, 362:598-602, 2018

PubMed Abstract: Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza virus hemagglutinin to generate multidomain antibodies with impressive breadth and potency. Multidomain antibody MD3606 protects mice against influenza A and B infection when administered intravenously or expressed locally from a recombinant adeno-associated virus vector. Crystal and single-particle electron microscopy structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multidomain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus-mediated gene delivery, they may provide an effective strategy to prevent infection with influenza virus and other highly variable pathogens.

PubMed: 30385580
DOI: 10.1126/science.aaq0620

Experimental method

X-RAY DIFFRACTION (2.05 Å)