The thermodynamics of Pr55Gag-RNA interaction regulate the assembly of HIV Tanwar, Hanumantsingh, Khoo, Keith K., Garvey, Megan, Waddington, Lynne, Leis, Andrew, Hijnen, Marcel, Velkov, Tony, Dumsday, Geoff J., McKinstry, William J. and Mak, Johnson 2017, The thermodynamics of Pr55Gag-RNA interaction regulate the assembly of HIV, PLoS pathogens, vol. 13, no. 2, pp. 1-24, doi: 10.0.5.91/journal.ppat.1006221. Attached Files Name Description MIMEType Size Downloads tanwar-thermodynamics-2017.pdf Published version application/pdf 2.48MB 21 Title The thermodynamics of Pr55Gag-RNA interaction regulate the assembly of HIV Author(s) Tanwar, Hanumantsingh Khoo, Keith K. Garvey, Megan Waddington, Lynne Leis, Andrew Hijnen, Marcel Velkov, Tony Dumsday, Geoff J. McKinstry, William J. Mak, Johnson orcid.org/0000-0002-5229-5707 Journal name PLoS pathogens Volume number 13 Issue number 2 Article ID e1006221 Start page 1 End page 24 Total pages 24 Publisher Public Library of Science Place of publication San Francisco, Calif. Publication date 2017-02-21 ISSN 1553-7366 Summary The interactions that occur during HIV Pr55Gag oligomerization and genomic RNA packagingare essential elements that facilitate HIV assembly. However, mechanistic details ofthese interactions are not clearly defined. Here, we overcome previous limitations in producinglarge quantities of full-length recombinant Pr55Gag that is required for isothermal titrationcalorimetry (ITC) studies, and we have revealed the thermodynamic properties of HIVassembly for the first time. Thermodynamic analysis showed that the binding between RNAand HIV Pr55Gag is an energetically favourable reaction (ΔG<0) that is further enhanced bythe oligomerization of Pr55Gag. The change in enthalpy (ΔH) widens sequentially from: (1)Pr55Gag-Psi RNA binding during HIV genome selection; to (2) Pr55Gag-Guanosine Uridine(GU)-containing RNA binding in cytoplasm/plasma membrane; and then to (3) Pr55Gag-Adenosine(A)-containing RNA binding in immature HIV. These data imply the stepwiseincrements of heat being released during HIV biogenesis may help to facilitate the processof viral assembly. By mimicking the interactions between A-containing RNA and oligomericPr55Gag in immature HIV, it was noted that a p6 domain truncated Pr50Gag Δp6 is less efficientthan full-length Pr55Gag in this thermodynamic process. These data suggest a potentialunknown role of p6 in Pr55Gag-Pr55Gag oligomerization and/or Pr55Gag-RNA interaction duringHIV assembly. Our data provide direct evidence on how nucleic acid sequences and theoligomeric state of Pr55Gag regulate HIV assembly. Language eng DOI 10.0.5.91/journal.ppat.1006221 Field of Research 110804 Medical Virology 110802 Medical Infection Agents (incl Prions) 0605 Microbiology 1107 Immunology 1108 Medical Microbiology Socio Economic Objective 920109 Infectious Diseases HERDC Research category C1 Refereed article in a scholarly journal ERA Research output type C Journal article Copyright notice ©2017, The Authors Free to Read? Yes Use Rights Persistent URL http://hdl.handle.net/10536/DRO/DU:30091566 Document type: Journal Article Collections: School of Medicine Open Access Collection Related Links Link Description Connect to published version Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au. Versions Version Filter Type Wed, 01 Mar 2017, 08:08:16 EST Fri, 24 Mar 2017, 15:16:40 EST Sat, 25 Mar 2017, 04:00:06 EST Mon, 27 Mar 2017, 07:08:42 EST Sat, 01 Apr 2017, 01:31:48 EST Fri, 14 Apr 2017, 06:06:38 EST Wed, 14 Jun 2017, 15:43:50 EST Wed, 14 Jun 2017, 15:47:02 EST Wed, 14 Jun 2017, 15:52:38 EST Filtered Full Citation counts:   Cited 1 times in TR Web of Science Cited 4 times in Scopus Search Google Scholar Access Statistics: 73 Abstract Views, 22 File Downloads  -  Detailed Statistics Created: Fri, 24 Mar 2017, 15:16:40 EST

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