7KC1

Cryo-EM structure of SRR2899884.46167H+MEDI8852L fab in complex with Victoria HA

Summary for 7KC1

• Entry DOI: 10.2210/pdb7kc1/pdb
• EMDB information: 22804
• Descriptor: Hemagglutinin, Fusion protein of Hemagglutinin and Envelope glycoprotein, Fab heavy chain, ... (7 entities in total)
• Functional Keywords: flu, ha, hv6-1, vrc, immune system, immune system-viral protein complex
• Biological source: Influenza A virus; More
• Total number of polymer chains: 12
• Total formula weight: 344828.60

Authors

Gorman, J.,Kwong, P.D. (deposition date: 2020-10-04, release date: 2021-05-12, Last modification date: 2024-11-20)

Primary citation

Chuang, G.Y.,Shen, C.H.,Cheung, C.S.,Gorman, J.,Creanga, A.,Joyce, M.G.,Leung, K.,Rawi, R.,Wang, L.,Yang, E.S.,Yang, Y.,Zhang, B.,Zhang, Y.,Kanekiyo, M.,Zhou, T.,DeKosky, B.J.,Graham, B.S.,Mascola, J.R.,Kwong, P.D.
Sequence-Signature Optimization Enables Improved Identification of Human HV6-1-Derived Class Antibodies That Neutralize Diverse Influenza A Viruses.
Front Immunol, 12:662909-662909, 2021

PubMed Abstract: Sequence signatures of multidonor broadly neutralizing influenza antibodies can be used to quantify the prevalence of B cells with virus-neutralizing potential to accelerate development of broadly protective vaccine strategies. Antibodies of the same class share similar recognition modes and developmental pathways, and several antibody classes have been identified that neutralize diverse group 1- and group 2-influenza A viruses and have been observed in multiple human donors. One such multidonor antibody class, the HV6-1-derived class, targets the stem region of hemagglutinin with extraordinary neutralization breadth. Here, we use an iterative process to combine informatics, biochemical, and structural analyses to delineate an improved sequence signature for HV6-1-class antibodies. Based on sequence and structure analyses of known HV6-1 class antibodies, we derived a more inclusive signature (version 1), which we used to search for matching B-cell transcripts from published next-generation sequencing datasets of influenza vaccination studies. We expressed selected antibodies, evaluated their function, and identified amino acid-level requirements from which to refine the sequence signature (version 2). The cryo-electron microscopy structure for one of the signature-identified antibodies in complex with hemagglutinin confirmed motif recognition to be similar to known HV6-1-class members, MEDI8852 and 56.a.09, despite differences in recognition-loop length. Threading indicated the refined signature to have increased accuracy, and signature-identified heavy chains, when paired with the light chain of MEDI8852, showed neutralization comparable to the most potent members of the class. Incorporating sequences of additional class members thus enables an improved sequence signature for HV6-1-class antibodies, which can identify class members with increased accuracy.

PubMed: 34135892
DOI: 10.3389/fimmu.2021.662909

Experimental method

ELECTRON MICROSCOPY (3.41 Å)