The Late-Domain-Containing Protein p6 Is the Predominant Phosphoprotein of Human Immunodeficiency Virus Type 1 Particles

Müller, Bárbara; Patschinsky, T; Kräusslich, Hans‐Georg

doi:10.1128/jvi.76.3.1015-1024.2002

Cited by 51 publications

(59 citation statements)

References 67 publications

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“…In HIV-1 particles, p6 also exist as a highly phosphorylated protein that is modified at Ser, Thr, and Tyr residues (20). Subsequently, it was shown that p6 becomes phosphorylated at position Thr-23 by the cellular mitogen-activated protein kinase ERK-2, which is also incorporated into mature virions, and appears to regulate L-domain function of p6 (21).…”

Section: Discussionmentioning

confidence: 99%

“…It has also been implicated in the incorporation of the viral Pol and Env proteins (16,17) and in the control of particle size (18,19). Recently, p6 was reported to be the major phosphoprotein of HIV-1 particles (20), and there is evidence that the host cell mitogen-activated protein kinase ERK-2 regulates viral assembly and release by phosphorylation of Thr-23 in p6 (21).…”

mentioning

confidence: 99%

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Solution Structure of the Human Immunodeficiency Virus Type 1 p6 Protein

Fossen

Wray

Bruns

et al. 2005

Journal of Biological Chemistry

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The human immunodeficiency virus type 1 p6 protein represents a docking site for several cellular and viral binding factors and fulfills major roles in the formation of infectious viruses. To date, however, the structure of this 52-amino acid protein, by far the smallest lentiviral protein known, either in its mature form as free p6 or as the C-terminal part of the Pr55 Gag polyprotein has not been unraveled. We have explored the high resolution structure and folding of p6 by CD and NMR spectroscopy. Under membranous solution conditions, p6 can adopt a helix-flexible helix structure; a short helix-1 (amino acids 14 -18) is connected to a pronounced helix-2 (amino acids 33-44) by a flexible hinge region. Thus, p6 can be subdivided into two distinct structural and functional domains; helix-2 perfectly defines the region that binds to the virus budding factor AIP-1/ALIX, indicating that this structure is required for interaction with the endosomal sorting complex required for transport. The PTAP motif at the N terminus, comprising the primary late assembly domain, which is crucial for interaction with another cellular budding factor, Tsg101, does not exhibit secondary structure. However, the adjacent helix-1 may play an indirect role in the specific complex formation between p6 and the binding groove in Tsg101. Moreover, binding studies by NMR demonstrate that helix-2, which also comprises the LXXLF motif required for incorporation of the human immunodeficiency virus type 1 accessory protein Vpr into budding virions, specifically interacts with the Vpr binding region, indicating that under the specific solution conditions used for structure analysis, p6 adopted a functional conformation.The main structural components of retrovirus particles are synthesized as three polyproteins that produce either the virion interior (Gag), the viral enzymes (Pol), or the glycoproteins of the virion envelope (Env). The Gag polyprotein is required and sufficient for virus particle assembly and budding, although genomic RNA and envelope proteins are obligatory for production of infectious progeny virions. The processing of the HIV-1 Gag polyprotein Pr55 by the viral protease generates the matrix, capsid, nucleocapsid (NC), and p6 proteins. Matrix mediates the plasma membrane targeting of Gag and lines the inner shell of the mature virus particle, capsid forms the conical core shell encasing NC, and NC regulates packaging and condensation of the viral genome (1-6). The role of p6 during virus entry and its location in mature HIV-1 2 virus particles are not known, although it appears not to be associated with the virus core (7,8). Several functions, however, have been ascribed to p6. It facilitates virus budding (9 -11) and is required for the incorporation of the viral accessory protein Vpr into the virus particle (12-15). It has also been implicated in the incorporation of the viral Pol and Env proteins (16,17) and in the control of particle size (18,19). Recently, p6 was reported to be the major phosphoprotein of HIV-1 particles (20...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Solution Structure of the Human Immunodeficiency Virus Type 1 p6 Protein

Fossen

Wray

Bruns

et al. 2005

Journal of Biological Chemistry

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“…High titer HIV-1 preparations (ϳ10 9 infectious units/ml) containing minimal cellular contaminants were obtained from acutely infected MT-4 cells and purified by velocity gradient centrifugation (36). The purity of the sample was evaluated on silver-stained SDS gels, which showed that the Gag proteins were the main constituents and demonstrated minimal contamination with cellular proteins (data not shown) (55).…”

Section: Tsg101 Proteins Lacking the Vps28-binding Site Fail Tomentioning

confidence: 99%

The Human Endosomal Sorting Complex Required for Transport (ESCRT-I) and Its Role in HIV-1 Budding

Stuchell

Garrus

Müller

et al. 2004

Journal of Biological Chemistry

147

152

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“…HIV-1 virions were found to contain several phosphoproteins including MAp17 gag (13), CAp24 gag (14), and recently p6 gag proteins (15).…”

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confidence: 99%

Active cAMP-dependent Protein Kinase Incorporated within Highly Purified HIV-1 Particles Is Required for Viral Infectivity and Interacts with Viral Capsid Protein

Cartier¹,

Hemonnot²,

Gay

et al. 2003

Journal of Biological Chemistry

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Host cell components, including protein kinases such as ERK-2/mitogen-activated protein kinase, incorporated within human immunodeficiency virus type 1 (HIV-1) virions play a pivotal role in the ability of HIV to infect and replicate in permissive cells. The present work provides evidence that the catalytic subunit of cAMP-dependent protein kinase (C-PKA) is packaged within HIV-1 virions as demonstrated using purified subtilisin-digested viral particles. Virus-associated C-PKA was shown to be enzymatically active and able to phosphorylate synthetic substrate in vitro. Suppression of virion-associated C-PKA activity by specific synthetic inhibitor had no apparent effect on viral precursor maturation and virus assembly. However, virus-associated C-PKA activity was demonstrated to regulate HIV-1 infectivity as assessed by single round infection assays performed by using viruses produced from cells expressing an inactive form of C-PKA. In addition, virus-associated C-PKA was found to co-precipitate with and to phosphorylate the CAp24 gag protein. Altogether our results indicate that virus-associated C-PKA regulates HIV-1 infectivity, possibly by catalyzing phosphorylation of the viral CAp24 gag protein.

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The Late-Domain-Containing Protein p6 Is the Predominant Phosphoprotein of Human Immunodeficiency Virus Type 1 Particles

Cited by 51 publications

References 67 publications

Solution Structure of the Human Immunodeficiency Virus Type 1 p6 Protein

Solution Structure of the Human Immunodeficiency Virus Type 1 p6 Protein

The Human Endosomal Sorting Complex Required for Transport (ESCRT-I) and Its Role in HIV-1 Budding

Active cAMP-dependent Protein Kinase Incorporated within Highly Purified HIV-1 Particles Is Required for Viral Infectivity and Interacts with Viral Capsid Protein

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