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5cjs

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Crystal structure of a monomeric influenza hemagglutinin stem in complex with an broadly neutralizing antibody CR9114

Structural highlights

5cjs is a 8 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 4.3Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

The identification of human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem revitalized hopes of developing a universal influenza vaccine. Using a rational design and library approach, we engineered stable HA stem antigens ('mini-HAs') based on an H1 subtype sequence. Our most advanced candidate exhibits structural and bnAb binding properties comparable to full-length HA, completely protects mice in lethal heterologous and heterosubtypic challenge models, and reduces fever following sublethal challenge in cynomolgus monkeys. Antibodies elicited by this mini-HA in mice and nonhuman primates bind a wide range of HAs, compete with human bnAbs for HA stem binding, neutralize H5N1 viruses, and mediate antibody-dependent effector activity. These results provide proof-of-concept for design of HA stem mimics that elicit bnAbs against influenza A group 1 viruses.

A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen.,Impagliazzo A, Milder F, Kuipers H, Wagner M, Zhu X, Hoffman RM, van Meersbergen R, Huizingh J, Wanningen P, Verspuij J, de Man M, Ding Z, Apetri A, Kukrer B, Sneekes-Vriese E, Tomkiewicz D, Laursen NS, Lee PS, Zakrzewska A, Dekking L, Tolboom J, Tettero L, van Meerten S, Yu W, Koudstaal W, Goudsmit J, Ward AB, Meijberg W, Wilson IA, Radosevic K Science. 2015 Aug 24. pii: aac7263. PMID:26303961^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Impagliazzo A, Milder F, Kuipers H, Wagner M, Zhu X, Hoffman RM, van Meersbergen R, Huizingh J, Wanningen P, Verspuij J, de Man M, Ding Z, Apetri A, Kukrer B, Sneekes-Vriese E, Tomkiewicz D, Laursen NS, Lee PS, Zakrzewska A, Dekking L, Tolboom J, Tettero L, van Meerten S, Yu W, Koudstaal W, Goudsmit J, Ward AB, Meijberg W, Wilson IA, Radosevic K. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science. 2015 Aug 24. pii: aac7263. PMID:26303961 doi:http://dx.doi.org/10.1126/science.aac7263