Behaviour of single transmembrane peptides during in meso crystallization from the contrast-matched lipidic cubic phase of monoolein

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dc.contributor.authorvan't Hag, Len_AU
dc.contributor.authorde Campo, Len_AU
dc.contributor.authorTran, Nen_AU
dc.contributor.authorSokolova, AVen_AU
dc.contributor.authorTrenker, Ren_AU
dc.contributor.authorCall, Men_AU
dc.contributor.authorGarvey, CJen_AU
dc.contributor.authorLeung., Aen_AU
dc.contributor.authorDarwish, TAen_AU
dc.contributor.authorKrause-Heuer, AMen_AU
dc.contributor.authorKnott, RBen_AU
dc.contributor.authorMeikle, Ten_AU
dc.contributor.authorGras, Sen_AU
dc.contributor.authorDrummond, CJen_AU
dc.contributor.authorMezzenga, Ren_AU
dc.contributor.authorConn, Cen_AU
dc.date.accessioned2023-11-22T20:50:06Zen_AU
dc.date.available2023-11-22T20:50:06Zen_AU
dc.date.issued2018-11-19en_AU
dc.date.statistics2023-07-05en_AU
dc.description.abstractIn meso membrane protein crystallization within a lipidic mesophase has revolutionized the structural biology of integral membrane proteins (IMPs). High-resolution structures of these proteins are crucial to understanding fundamental cellular processes at a molecular level, and can lead to new and improved treatments for a wide range of diseases via rational drug design. However, overall success rates of the promising in meso crystallization technique remain low because of a fundamental lack of understanding about factors that promote crystal growth. In particular, to date, two decades from invention of the method, the protein-eye-view of the in meso crystallization mechanism had not been solved. We have investigated this for the first time using small-angle neutron scattering (SANS). Contrast-matching between the scattering of the lipid membrane formed by MO and the aqueous solution was used to isolate and track the scattering of single-transmembrane peptides during the growth of protein crystals in meso. No peptide enrichment was observed at the flat points of the diamond cubic QIID phase of MO in contrast to suggestions in several modeling studies. During in meso crystallization of the DAP12 peptide a decrease in form factor and a transient fluid lamellar Lα phase could be observed providing direct evidence for the proposed crystallization mechanism. Synthesis of fully deuterated MO was required for this purpose and scattering of this new material in various solvents and under a range of conditions will be described, specifically regarding the effect of the relative scattering length densities (SLD) of the headgroup, acyl chain and solvent, which can advance the use of neutron scattering with other self-assembly materials. © The Authors.en_AU
dc.identifier.citationvan ’t Hag, L., de Campo, L., Tran, N., Sokolova, A., Trenker, R., Call, M., Garvey, C., Leung., A., Darwish, T., Krause-Heuer, A., Knott, R., Meikle, T., Gras, S., Drummond, C., Mezzenga, R., & Conn, C. (2018). Behaviour of single transmembrane peptides during in meso crystallization from the contrast-matched lipidic cubic phase of monoolein. Keynote presented at ANBUG-AINSE Neutron Scattering Symposium, AANSS 2018, AINSE Conference Centre New Illawarra Road Lucas Heights NSW 2234, Australia, Monday 19 November 2018 - Wednesday 21 November 2018, (pp. 19 - 20). Retrieved from https://events01.synchrotron.org.au/event/84/book-of-abstracts.pdfen_AU
dc.identifier.conferenceenddate2018-11-21en_AU
dc.identifier.conferencenameANBUG-AINSE Neutron Scattering Symposium, AANSS 2018en_AU
dc.identifier.conferenceplaceLucas Heights, New South Walesen_AU
dc.identifier.conferencestartdate2018-11-19en_AU
dc.identifier.pagination19-20en_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/15231en_AU
dc.language.isoenen_AU
dc.publisherAustralian Institute of Nuclear Science and Engineering (AINSE)en_AU
dc.relation.urihttps://events01.synchrotron.org.au/event/84/book-of-abstracts.pdfen_AU
dc.subjectMembrane proteinsen_AU
dc.subjectCrystallizationen_AU
dc.subjectDrugsen_AU
dc.subjectSmall angle scatteringen_AU
dc.subjectNeutronsen_AU
dc.subjectScatteringen_AU
dc.subjectPeptidesen_AU
dc.titleBehaviour of single transmembrane peptides during in meso crystallization from the contrast-matched lipidic cubic phase of monooleinen_AU
dc.typeConference Presentationen_AU
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