Crystal structures of Uso1 membrane tether reveal an alternative conformation in the globular head domain

The preparation and purification of [Pt( hpip )Cl2] and [Pd( hpip )Cl2] ( hpip = homopiperazine = 1,4-diazacycloheptane) are described. Crystal structures of [Pt( hpip )Cl2] and [Pd( hpip )Cl2] have been determined by X-ray diffraction methods and refined to R values of 0.023 (932 F) and 0.023 (948 F). The crystals of [Pt( hpip )Cl2] are orthorhombic, space group Pbcm , a 7.7019(8), b 9.8080(12), c 12.1944(14) Ǻ, and those of [Pd( hpip )Cl2] are monoclinic, space group P21/m, a 6.1001(9), b 11.527(2), c 6.458(I) Ǻ, β 106.30(2)°. The seven- membered rings of the ligands in both complexes adopt boat-like conformations in which the five- membered chelate ring has an eclipsed N-C-C-N group and the six- membered chelate ring adopts a chair conformation. Molecular mechanics methods were used to investigate whether this conformation was a crystallographic artefact but it was found to be real. An alternative conformation in which the six-membered chelate ring adopts a skew-boat conformation was also investigated. It was found to be less stable than the conformation observed in the crystal structures, but to a degree that depends on whether non-bonded interactions involving the metal atom were included or not.

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Improved specificity and reduced subtype cross-reactivity for antibody detection by ELISA using globular head domain recombinant hemagglutinin

Journal of Virological Methods ◽

10.1016/j.jviromet.2014.09.006 ◽

2014 ◽

Vol 209 ◽

pp. 121-125 ◽

Cited By ~ 6

Author(s):

Zhu-Nan Li ◽

Paul J. Carney ◽

Seh-Ching Lin ◽

Ji Li ◽

Jessie C. Chang ◽

...

Keyword(s):

Cross Reactivity ◽

Antibody Detection ◽

Head Domain ◽

Recombinant Hemagglutinin ◽

Globular Head

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Protective Immunity Based on the Conserved Hemagglutinin Stalk Domain and Its Prospects for Universal Influenza Vaccine Development

BioMed Research International ◽

10.1155/2014/546274 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 24

Author(s):

Madhu Khanna ◽

Sachin Sharma ◽

Binod Kumar ◽

Roopali Rajput

Keyword(s):

Influenza Virus ◽

Influenza Vaccine ◽

Natural Infection ◽

Influenza Viruses ◽

Cross Protection ◽

Influenza B ◽

Universal Vaccine ◽

Virus Surface ◽

Head Domain ◽

Globular Head

Influenza virus surface glycoprotein hemagglutinin (HA) is an excellent and chief target thatelicitsneutralizing antibodies during vaccination or natural infection. Its HA2 subunit (stem domain) is most conserved as compared to HA1 subunit (globular head domain). Current influenza vaccine relies on globular head domain that provides protection only against the homologous vaccine strains, rarely provides cross-protection against divergent strains, and needs to be updated annually. There is an urge for a truly universal vaccine that provides broad cross-protection against different subtype influenza A viruses along with influenza B viruses and need not be updated annually. Antibodies against the stem domain of hemagglutinin (HA) are able to neutralize a wide spectrum of influenza virus strains and subtypes. These stem-specific antibodies have great potential for the development of universal vaccine against influenza viruses. In this review, we have discussed the stem-specific cross-reactive antibodies and heterosubtypic protection provided by them. We have also discussed their epitope-based DNA vaccine and their future prospects in this scenario.

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gAd-globular Head Domain of Adiponectin Increases Fatty Acid Oxidation in Newborn Rabbit Hearts

Journal of Biological Chemistry ◽

10.1074/jbc.m400347200 ◽

2004 ◽

Vol 279 (43) ◽

pp. 44320-44326 ◽

Cited By ~ 33

Author(s):

Arzu Onay-Besikci ◽

Judith Y. Altarejos ◽

Gary D. Lopaschuk

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Acid Oxidation ◽

Newborn Rabbit ◽

Head Domain ◽

Globular Head

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Hemagglutinin Stalk- and Neuraminidase-Specific Monoclonal Antibodies Protect against Lethal H10N8 Influenza Virus Infection in Mice

Journal of Virology ◽

10.1128/jvi.02275-15 ◽

2015 ◽

Vol 90 (2) ◽

pp. 851-861 ◽

Cited By ~ 38

Author(s):

Teddy John Wohlbold ◽

Veronika Chromikova ◽

Gene S. Tan ◽

Philip Meade ◽

Fatima Amanat ◽

...

Keyword(s):

Influenza Virus ◽

Monoclonal Antibodies ◽

Virus Infection ◽

Influenza Virus Infection ◽

Influenza Viruses ◽

Morbidity And Mortality ◽

Head Domain ◽

Group 2 ◽

Reactive Antibody ◽

Globular Head

ABSTRACTBetween November 2013 and February 2014, China reported three human cases of H10N8 influenza virus infection in the Jiangxi province, two of which were fatal. Using hybridoma technology, we isolated a panel of H10- and N8-directed monoclonal antibodies (MAbs) and further characterized the binding reactivity of these antibodies (via enzyme-linked immunosorbent assay) to a range of purified virus and recombinant protein substrates. The H10-directed MAbs displayed functional hemagglutination inhibition (HI) and neutralization activity, and the N8-directed antibodies displayed functional neuraminidase inhibition (NI) activity against H10N8. Surprisingly, the HI-reactive H10 antibodies, as well as a previously generated, group 2 hemagglutinin (HA) stalk-reactive antibody, demonstrated NI activity against H10N8 and an H10N7 strain; this phenomenon was absent when virus was treated with detergent, suggesting the anti-HA antibodies inhibited neuraminidase enzymatic activity through steric hindrance. We tested the prophylactic efficacy of one representative H10-reactive, N8-reactive, and group 2 HA stalk-reactive antibodyin vivousing a BALB/c challenge model. All three antibodies were protective at a high dose (5 mg/kg). At a low dose (0.5 mg/kg), only the anti-N8 antibody prevented weight loss. Together, these data suggest that antibody targets other than the globular head domain of the HA may be efficacious in preventing influenza virus-induced morbidity and mortality.IMPORTANCEAvian H10N8 and H10N7 viruses have recently crossed the species barrier, causing morbidity and mortality in humans and other mammals. Although these reports are likely isolated incidents, it is possible that more cases may emerge in future winter seasons, similar to H7N9. Furthermore, regular transmission of avian influenza viruses to humans increases the risk of adaptive mutations and reassortment events, which may result in a novel virus with pandemic potential. Currently, no specific therapeutics or vaccines are available against the H10N8 influenza virus subtype. We generated a panel of H10- and N8-reactive MAbs. Although these antibodies may practically be developed into therapeutic agents, characterizing the protective potential of MAbs that have targets other than the HA globular head domain will provide insight into novel antibody-mediated mechanisms of protection and help to better understand correlates of protection for influenza A virus infection.

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