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Structural characterization of a fusion glycoprotein from a retrovirus that undergoes a hybrid 2-step entry mechanism.

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Aydin H, Smrke BM, Lee JE
OpenAccess logo FASEB J 27 5059-71 (2013)
Cited: 11 times
EuropePMC logo PMID: 24036886

Abstract

Entry of enveloped viruses into host cells is mediated by their surface envelope glycoproteins (Env). On the surface of the virus, Env is in a metastable, prefusion state, primed to catalyze the fusion of the viral and host membranes. An external trigger is needed to promote the drastic conformational changes necessary for the fusion subunit to fold into the low-energy, 6-helix bundle. These triggers typically facilitate pH-independent entry at the plasma membrane or pH-dependent entry in a low-pH endosomal compartment. The α-retrovirus avian sarcoma leukosis virus (ASLV) has a rare, 2-step entry mechanism with both pH-dependent and pH-independent features. Here, we present the 2.0-Å-resolution crystal structure of the ASLV transmembrane (TM) fusion protein. Our structural and biophysical studies indicated that unlike other pH-dependent or pH-independent viral TMs, the ASLV fusion subunit is stable irrespective of pH. Two histidine residues (His490 and His492) in the chain reversal region confer stability at low pH. A structural comparison of class I viral fusion proteins suggests that the presence of a positive charge, either a histidine or arginine amino acid, stabilizes a helical dipole moment and is a signature of fusion proteins active at low pH. The structure now reveals key residues and features that explain its 2-step mechanism, and we discuss the implications of the ASLV TM structure in the context of general mechanisms required for membrane fusion.

Reviews - 4jpr mentioned but not cited (1)

  1. A Frame-by-Frame Glance at Membrane Fusion Mechanisms: From Viral Infections to Fertilization. Azimi FC, Dean TT, Minari K, Basso LGM, Vance TDR, Serrão VHB. Biomolecules 13 1130 (2023)

Articles - 4jpr mentioned but not cited (2)

  1. Structural characterization of a fusion glycoprotein from a retrovirus that undergoes a hybrid 2-step entry mechanism. Aydin H, Smrke BM, Lee JE. FASEB J 27 5059-5071 (2013)
  2. Electrostatic Architecture of the Infectious Salmon Anemia Virus (ISAV) Core Fusion Protein Illustrates a Carboxyl-Carboxylate pH Sensor. Cook JD, Soto-Montoya H, Korpela MK, Lee JE. J Biol Chem 290 18495-18504 (2015)


Reviews citing this publication (1)

  1. Fusion of Enveloped Viruses in Endosomes. White JM, Whittaker GR. Traffic 17 593-614 (2016)

Articles citing this publication (7)

  1. Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques. Santra S, Tomaras GD, Warrier R, Nicely NI, Liao HX, Pollara J, Liu P, Alam SM, Zhang R, Cocklin SL, Shen X, Duffy R, Xia SM, Schutte RJ, Pemble Iv CW, Dennison SM, Li H, Chao A, Vidnovic K, Evans A, Klein K, Kumar A, Robinson J, Landucci G, Forthal DN, Montefiori DC, Kaewkungwal J, Nitayaphan S, Pitisuttithum P, Rerks-Ngarm S, Robb ML, Michael NL, Kim JH, Soderberg KA, Giorgi EE, Blair L, Korber BT, Moog C, Shattock RJ, Letvin NL, Schmitz JE, Moody MA, Gao F, Ferrari G, Shaw GM, Haynes BF. PLoS Pathog 11 e1005042 (2015)
  2. Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: insights into mechanisms of general viral fusion and inhibitor design. Aydin H, Al-Khooly D, Lee JE. Protein Sci 23 603-617 (2014)
  3. Retroviral host range extension is coupled with Env-activating mutations resulting in receptor-independent entry. Lounková A, Kosla J, Přikryl D, Štafl K, Kučerová D, Svoboda J. Proc Natl Acad Sci U S A 114 E5148-E5157 (2017)
  4. The Bipartite Sequence Motif in the N and C Termini of gp85 of Subgroup J Avian Leukosis Virus Plays a Crucial Role in Receptor Binding and Viral Entry. Zhang Y, Yu M, Xing L, Liu P, Chen Y, Chang F, Wang S, Bao Y, Farooque M, Li X, Guan X, Liu Y, Liu A, Qi X, Pan Q, Zhang Y, Gao L, Li K, Liu C, Cui H, Wang X, Gao Y. J Virol 94 e01232-20 (2020)
  5. X-ray Structures of the Post-fusion 6-Helix Bundle of the Human Syncytins and their Functional Implications. Ruigrok K, Vaney MC, Buchrieser J, Baquero E, Hellert J, Baron B, England P, Schwartz O, Rey FA, Backovic M. J Mol Biol 431 4922-4940 (2019)
  6. Structure of the Core Postfusion Porcine Endogenous Retrovirus Fusion Protein. Dean TT, Serrão VHB, Lee JE. mBio 13 e0292021 (2022)
  7. On board a raft or boat in the retrovirus sea. Svoboda J. Proc Natl Acad Sci U S A 113 3927-3931 (2016)


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