ALBERT

Description: Lambda-like double-stranded (ds) DNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm of pressure during genome packaging. The extensive integration between subunits in capsids requires the formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Although various mature capsids have been characterized at atomic resolution, no such procapsid structure is available for a dsDNA virus or bacteriophage. Here we present a procapsid X-ray structure at 3.65 A resolution, termed prohead II, of the lambda-like bacteriophage HK97, the mature capsid structure of which was previously solved to 3.44 A (ref. 2). A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and hydrogen/deuterium exchange data presented here demonstrate that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and beta-sheet regions. We also identified subunit interactions at each three-fold axis of the capsid that are maintained throughout maturation. The interactions sustain capsid integrity during subunit refolding and provide a fixed hinge from which subunits undergo rotational and translational motions during maturation. Previously published calorimetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90 kJ mol(-1) of energy. We propose that the major tertiary changes presented in this study reveal a structural basis for an exothermic maturation process probably present in many dsDNA bacteriophage and possibly viruses such as herpesvirus, which share the HK97 subunit fold.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765791/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765791/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gertsman, Ilya -- Gan, Lu -- Guttman, Miklos -- Lee, Kelly -- Speir, Jeffrey A -- Duda, Robert L -- Hendrix, Roger W -- Komives, Elizabeth A -- Johnson, John E -- GM08326/GM/NIGMS NIH HHS/ -- R01 AI040101/AI/NIAID NIH HHS/ -- R01 AI040101-04/AI/NIAID NIH HHS/ -- R01 AI040101-14/AI/NIAID NIH HHS/ -- R01 AI40101/AI/NIAID NIH HHS/ -- R01 GM47795/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Apr 2;458(7238):646-50. doi: 10.1038/nature07686. Epub 2009 Feb 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19204733" target="_blank"〉PubMed〈/a〉

Description: A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation, BG505 SOSIP.664, induced NAbs potently against the sequence-matched tier 2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (tier 1) viruses. Tier 2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas tier 1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP.664, also induced a strong autologous tier 2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for the development of HIV-1 vaccines aimed at inducing bNAbs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498988/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498988/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanders, Rogier W -- van Gils, Marit J -- Derking, Ronald -- Sok, Devin -- Ketas, Thomas J -- Burger, Judith A -- Ozorowski, Gabriel -- Cupo, Albert -- Simonich, Cassandra -- Goo, Leslie -- Arendt, Heather -- Kim, Helen J -- Lee, Jeong Hyun -- Pugach, Pavel -- Williams, Melissa -- Debnath, Gargi -- Moldt, Brian -- van Breemen, Marielle J -- Isik, Gozde -- Medina-Ramirez, Max -- Back, Jaap Willem -- Koff, Wayne C -- Julien, Jean-Philippe -- Rakasz, Eva G -- Seaman, Michael S -- Guttman, Miklos -- Lee, Kelly K -- Klasse, Per Johan -- LaBranche, Celia -- Schief, William R -- Wilson, Ian A -- Overbaugh, Julie -- Burton, Dennis R -- Ward, Andrew B -- Montefiori, David C -- Dean, Hansi -- Moore, John P -- 280829/European Research Council/International -- HHSN27201100016C/PHS HHS/ -- P01 AI082362/AI/NIAID NIH HHS/ -- P51 OD011106/OD/NIH HHS/ -- P51OD011106/OD/NIH HHS/ -- R01 AI076105/AI/NIAID NIH HHS/ -- R01 AI084817/AI/NIAID NIH HHS/ -- R37 AI036082/AI/NIAID NIH HHS/ -- R56 AI084817/AI/NIAID NIH HHS/ -- T32 GM007266/GM/NIGMS NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):aac4223. doi: 10.1126/science.aac4223. Epub 2015 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA. Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands. jpm2003@med.cornell.edu rws2002@med.cornell.edu. ; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands. ; Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA. ; International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA. ; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ; International AIDS Vaccine Initiative, New York, NY 10004, USA. ; Pepscan Therapeutics, 8243RC Lelystad, Netherlands. ; Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA. ; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Boston, MA 02114, USA. ; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA. ; Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. ; Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative, New York, NY 10004, USA. Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Boston, MA 02114, USA. ; International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA. Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Boston, MA 02114, USA. ; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA. jpm2003@med.cornell.edu rws2002@med.cornell.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26089353" target="_blank"〉PubMed〈/a〉