Arginine in α-defensins: differential effects on bactericidal activity correspond to geometry of membrane curvature generation and peptide-lipid phase behavior

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dc.contributor.author Schmidt, Nathan W.
dc.contributor.author Tai, KP.
dc.contributor.author Kamdar, K.
dc.contributor.author Mishra, Abhijit
dc.contributor.author Lai, G.H.
dc.contributor.author Ouellette, A.J.
dc.contributor.author Wong, Gerard C. L.
dc.date.accessioned 2014-03-16T12:50:21Z
dc.date.available 2014-03-16T12:50:21Z
dc.date.issued 2012-06
dc.identifier.citation Mishra, Abhijit et al., “Arginine in α-defensins: differential effects on bactericidal activity correspond to geometry of membrane curvature generation and peptide-lipid phase behavior”, Journal of Biological Chemistry, DOI: 10.1074/jbc.M112.358721, vol. 287, no.26, June, 2012. en_US
dc.identifier.issn 0021-9258
dc.identifier.issn 1083-351X
dc.identifier.uri http://dx.doi.org/10.1074/jbc.M112.358721
dc.identifier.uri https://repository.iitgn.ac.in/handle/123456789/790
dc.description.abstract The conserved tridisulfide array of the α-defensin family imposes a common triple-stranded β-sheet topology on peptides that may have highly diverse primary structures, resulting in differential outcomes after targeted mutagenesis. In mouse cryptdin-4 (Crp4) and rhesus myeloid α-defensin-4 (RMAD4), complete substitutions of Arg with Lys affect bactericidal peptide activity very differently. Lys-for-Arg mutagenesis attenuates Crp4, but RMAD4 activity remains mostly unchanged. Here, we show that the differential biological effect of Lys-for-Arg replacements can be understood by the distinct phase behavior of the experimental peptide-lipid system. In Crp4, small-angle x-ray scattering analyses showed that Arg-to-Lys replacements shifted the induced nanoporous phases to a different range of lipid compositions compared with the Arg-rich native peptide, consistent with the attenuation of bactericidal activity by Lys-for-Arg mutations. In contrast, such phases generated by RMAD4 were largely unchanged. The concordance between small-angle x-ray scattering measurements and biological activity provides evidence that specific types of α-defensin-induced membrane curvature-generating tendencies correspond directly to bactericidal activity via membrane destabilization. en_US
dc.description.statementofresponsibility by Abhijit Mishra et al.,
dc.format.extent Vol. 287, No.26, pp. 21866-21872
dc.language.iso en en_US
dc.publisher American Society for Biochemistry and Molecular Biology en_US
dc.subject Biological effects en_US
dc.subject Defensins en_US
dc.subject Differential effect en_US
dc.subject Lipid composition en_US
dc.subject Membrane curvature en_US
dc.subject Membrane destabilization en_US
dc.subject Nano-porous en_US
dc.subject Primary structures en_US
dc.subject Small angle X ray scattering en_US
dc.title Arginine in α-defensins: differential effects on bactericidal activity correspond to geometry of membrane curvature generation and peptide-lipid phase behavior en_US
dc.type Article en_US
dc.relation.journal Journal of Biological Chemistry


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