Structural role of the matrix protein of type D retroviruses in gag polyprotein stability and capsid assembly.

ABSTRACT Retroviral capsid assembly can occur by either of two distinct morphogenic processes: in type C viruses, the capsid assembles and buds at the plasma membrane, while in type B and D viruses, the capsid assembles within the cytoplasm and is then transported to the plasma membrane for budding. We have previously reported that a single-amino-acid substitution of a tryptophan for an arginine in the matrix protein (MA) of Mason-Pfizer monkey virus (MPMV) converts its capsid assembly from that of a type D retrovirus to that of the type C viruses (S. S. Rhee and E. Hunter, Cell 63:77–86, 1990). Here we identify a region of 18 amino acids within the MA of MPMV that is responsible for type D-specific morphogenesis. Insertion of these 18 amino acids into the MA of type C Moloney murine leukemia virus causes it to assemble an immature capsid in the cytoplasm. Furthermore, fusion of the MPMV MA to the green fluorescent protein resulted in altered intracellular targeting and a punctate accumulation of the fusion protein in the cytoplasm. These 18 amino acids, which are necessary and sufficient to target retroviral Gag polyproteins to defined sites in the cytoplasm, appear to define a novel mammalian cytoplasmic targeting/retention signal.

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SIRT1 activity orchestrates ECM expression during hESC-chondrogenic differentiation

10.1101/2020.05.12.087957 ◽

2020 ◽

Author(s):

Christopher A Smith ◽

Paul A Humphreys ◽

Nicola Bates ◽

Mark A Naven ◽

Stuart A Cain ◽

...

Keyword(s):

Matrix Protein ◽

Cell Function ◽

Epigenetic Modification ◽

Embryonic Stem ◽

Type Ii Collagen ◽

Cartilage Development ◽

The Matrix ◽

Col2a1 Expression ◽

Key Driver

AbstractEpigenetic modification is a key driver of differentiation and the deacetylase Sirtuin1 (SIRT1) is an established regulator of cell function, ageing and articular cartilage homeostasis. Here we investigate the role of SIRT1 during development of chondrocytes by using human embryonic stem cells (hESCs). HESC-chondroprogenitors were treated with SIRT1 activator; SRT1720, or inhibitor; EX527, at different development stages. Activation of SIRT1 during 3D-pellet culture led to significant increases in expression of ECM genes for type-II collagen (COL2A1) and aggrecan (ACAN), and chondrogenic transcription factors SOX5 and ARID5B, with SOX5 ChIP analysis demonstrating enrichment on the ACAN –10 enhancer. Unexpectedly, while ACAN was enhanced, GAG retention in the matrix was reduced when SIRT1 was activated. Significantly, ARID5B and COL2A1 were positively correlated, with Co-IP indicating association of ARID5B with SIRT1 suggesting that COL2A1 expression is promoted by an ARID5B and SIRT1 interaction. In conclusion, SIRT1 activation positively impacts on the expression of the main ECM proteins, whilst altering ECM composition and suppressing GAG content during cartilage development. These results suggest that SIRT1 activity can be beneficial to cartilage development and matrix protein synthesis but tailored by addition of other positive GAG mediators.

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A Conserved Tryptophan in the Ebola Virus Matrix Protein C-Terminal Domain Is Required for Efficient Virus-Like Particle Formation

Pathogens ◽

10.3390/pathogens9050402 ◽

2020 ◽

Vol 9 (5) ◽

pp. 402 ◽

Cited By ~ 1

Author(s):

Kristen A. Johnson ◽

Rudramani Pokhrel ◽

Melissa R. Budicini ◽

Bernard S. Gerstman ◽

Prem P. Chapagain ◽

...

Keyword(s):

Plasma Membrane ◽

Matrix Protein ◽

Ebola Virus ◽

Membrane Localization ◽

Virus Like Particles ◽

Plasma Membrane Localization ◽

The Matrix ◽

Dynamics Simulations

The Ebola virus (EBOV) harbors seven genes, one of which is the matrix protein eVP40, a peripheral protein that is sufficient to induce the formation of virus-like particles from the host cell plasma membrane. eVP40 can form different structures to fulfil different functions during the viral life cycle, although the structural dynamics of eVP40 that warrant dimer, hexamer, and octamer formation are still poorly understood. eVP40 has two conserved Trp residues at positions 95 and 191. The role of Trp95 has been characterized in depth as it serves as an important residue in eVP40 oligomer formation. To gain insight into the functional role of Trp191 in eVP40, we prepared mutations of Trp191 (W191A or W191F) to determine the effects of mutation on eVP40 plasma membrane localization and budding as well as eVP40 oligomerization. These in vitro and cellular experiments were complemented by molecular dynamics simulations of the wild-type (WT) eVP40 structure versus that of W191A. Taken together, Trp is shown to be a critical amino acid at position 191 as mutation to Ala reduces the ability of VP40 to localize to the plasma membrane inner leaflet and form new virus-like particles. Further, mutation of Trp191 to Ala or Phe shifted the in vitro equilibrium to the octamer form by destabilizing Trp191 interactions with nearby residues. This study has shed new light on the importance of interdomain interactions in stability of the eVP40 structure and the critical nature of timing of eVP40 oligomerization for plasma membrane localization and viral budding.

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Role of Matrix Protein in the Type D Retrovirus Replication Cycle: Importance of the Arginine Residue at Position 55

Virology ◽

10.1006/viro.1999.0179 ◽

2000 ◽

Vol 268 (2) ◽

pp. 533-538 ◽

Cited By ~ 12

Author(s):

Jiro Yasuda ◽

Eric Hunter

Keyword(s):

Matrix Protein ◽

Replication Cycle ◽

Arginine Residue ◽

Type D ◽

Retrovirus Replication

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A Single Amino Acid Deletion in the Matrix Protein of Porcine Reproductive and Respiratory Syndrome Virus Confers Resistance to a Polyclonal Swine Antibody with Broadly Neutralizing Activity

Journal of Virology ◽

10.1128/jvi.03287-14 ◽

2015 ◽

Vol 89 (12) ◽

pp. 6515-6520 ◽

Cited By ~ 31

Author(s):

Benjamin R. Trible ◽

Luca N. Popescu ◽

Nicholas Monday ◽

Jay G. Calvert ◽

Raymond R. R. Rowland

Keyword(s):

Amino Acid ◽

Matrix Protein ◽

Infectious Clone ◽

Virus Neutralization ◽

Single Amino Acid ◽

Respiratory Syndrome Virus ◽

Amino Acid Deletion ◽

Neutralizing Activity ◽

The Matrix

Assessment of virus neutralization (VN) activity in 176 pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) identified one pig with broadly neutralizing activity. A Tyr-10 deletion in the matrix protein provided escape from broad neutralization without affecting homologous neutralizing activity. The role of the Tyr-10 deletion was confirmed through an infectious clone with a Tyr-10 deletion. The results demonstrate differences in the properties and specificities of VN responses elicited during PRRSV infection.

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Functional and structural role of amino acid residues in the matrix α-helices, termini and cytosolic loops of the bovine mitochondrial oxoglutarate carrier

Biochimica et Biophysica Acta (BBA) - Bioenergetics ◽

10.1016/j.bbabio.2010.12.005 ◽

2011 ◽

Vol 1807 (3) ◽

pp. 302-310 ◽

Cited By ~ 18

Author(s):

Daniela V. Miniero ◽

Anna R. Cappello ◽

Rosita Curcio ◽

Anna Ludovico ◽

Lucia Daddabbo ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Residues ◽

Structural Role ◽

The Matrix ◽

Oxoglutarate Carrier

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An Immunohistochemical Study of Osteopontin in Pigment Gallstone Formation

The American Surgeon ◽

10.1177/000313481007600118 ◽

2010 ◽

Vol 76 (1) ◽

pp. 91-95

Author(s):

Motohiro Imano ◽

Takao Satou ◽

Tatsuki Itoh ◽

Yoshifumi Takeyama ◽

Atsushi Yasuda ◽

...

Keyword(s):

Calcium Binding ◽

Matrix Protein ◽

Bone Matrix ◽

Gallstone Formation ◽

Gallbladder Wall ◽

Gallbladder Epithelium ◽

Reticular Pattern ◽

The Matrix ◽

Pigment Gallstone

Mucin glycoproteins from the gallbladder epithelium are thought to contribute to the matrix or nucleus of gallstones and other biomineralization systems. The involved acidic glycoproteins have been reported in bile and gallstones. In addition, osteopontin (Opn) is a noncollagenous acidic bone matrix glycoprotein that possesses calcium-binding properties. To investigate the role of Opn in pigment gallstone formation, the involvement of Opn in pigment gallstone formation was studied immunohistochemically in the gallbladder wall and in the stones. Staining for Opn was strongly positive in the epithelium of stone-laden gallbladders and in their stones. The stone-laden gallbladders were infiltrated by macrophages, which intensely stained for Opn. Sections of the pigment stones, under low magnification, showed a lamellar pattern of Opn immunolabeling and showed a reticular pattern under high magnification. Our results indicate that Opn, an acidic glycoprotein from the gallbladder epithelium, seems to be involved in lithiasis. Opn from macrophages and/or the epithelium seems to help form the matrix protein.

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