scholarly journals The TRIM5α B-Box 2 Domain Promotes Cooperative Binding to the Retroviral Capsid by Mediating Higher-Order Self-Association

2008 ◽  
Vol 82 (23) ◽  
pp. 11495-11502 ◽  
Author(s):  
Xing Li ◽  
Joseph Sodroski
Keyword(s):  
Virus Entry ◽  
Coiled Coil ◽  
Higher Order ◽  
Restriction Factor ◽  
Cooperative Binding ◽  
Specific Function ◽  
Retroviral Infection ◽  
Spry Domain ◽  
Dense Arrays ◽  
Self Association

ABSTRACT The retroviral restriction factor, TRIM5α, blocks infection of a spectrum of retroviruses soon after virus entry into the cell. TRIM5α consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The B-box 2 domain is essential for retrovirus restriction by TRIM5α, but its specific function is unknown. We show here that the B-box 2 domain mediates higher-order self-association of TRIM5αrh oligomers. This self-association increases the efficiency of TRIM5α binding to the retroviral capsid, thus potentiating restriction of retroviral infection. The contribution of the B-box 2 domain to cooperative TRIM5α association with the retroviral capsid explains the conditional nature of the restriction phenotype exhibited by some B-box 2 TRIM5α mutants; the potentiation of capsid binding that results from B-box 2-mediated self-association is essential for restriction when B30.2(SPRY) domain-mediated interactions with the retroviral capsid are weak. Thus, B-box 2-dependent higher-order self-association and B30.2(SPRY)-dependent capsid binding represent complementary mechanisms whereby sufficiently dense arrays of capsid-bound TRIM5α proteins can be achieved.

scholarly journals Higher-order assembly of Sorting Nexin 16 controls tubulation and distribution of neuronal endosomes

2019 ◽  
Vol 218 (8) ◽  
pp. 2600-2618 ◽  
Author(s):  
ShiYu Wang ◽  
Zechuan Zhao ◽  
Avital A. Rodal
Keyword(s):  
Cell Body ◽  
Motor Neurons ◽  
Coiled Coil ◽  
Higher Order ◽  
Synaptic Growth ◽  
Sorting Nexin ◽  
Protein Receptors ◽  
Self Association ◽  
Signaling Receptors

The activities of neuronal signaling receptors depend heavily on the maturation state of the endosomal compartments in which they reside. However, it remains unclear how the distribution of these compartments within the uniquely complex morphology of neurons is regulated and how this distribution itself affects signaling. Here, we identified mechanisms by which Sorting Nexin 16 (SNX16) controls neuronal endosomal maturation and distribution. We found that higher-order assembly of SNX16 via its coiled-coil (CC) domain drives membrane tubulation in vitro and endosome association in cells. In Drosophila melanogaster motor neurons, activation of Rab5 and CC-dependent self-association of SNX16 lead to its endosomal enrichment, accumulation in Rab5- and Rab7-positive tubulated compartments in the cell body, and concomitant depletion of SNX16-positive endosomes from the synapse. This results in accumulation of synaptic growth–promoting bone morphogenetic protein receptors in the cell body and correlates with increased synaptic growth. Our results indicate that Rab regulation of SNX16 assembly controls the endosomal distribution and signaling activities of receptors in neurons.

scholarly journals A B-Box 2 Surface Patch Important for TRIM5α Self-Association, Capsid Binding Avidity, and Retrovirus Restriction

2009 ◽  
Vol 83 (20) ◽  
pp. 10737-10751 ◽  
Author(s):  
Felipe Diaz-Griffero ◽  
Xu-rong Qin ◽  
Fumiaki Hayashi ◽  
Takanori Kigawa ◽  
Andres Finzi ◽  
...  
Keyword(s):  
Coiled Coil ◽  
Higher Order ◽  
Surface Patch ◽  
Resonance Structure ◽  
Nuclear Magnetic Resonance Structure ◽  
Major Mechanism ◽  
Cytoplasmic Bodies ◽  
Surface Alteration ◽  
Self Association ◽  
Hiv 1

ABSTRACT TRIM5α is a tripartite motif (TRIM) protein that consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The TRIM5αrh protein from rhesus monkeys recognizes the human immunodeficiency virus type 1 (HIV-1) capsid as it enters the host cell and blocks virus infection prior to reverse transcription. HIV-1-restricting ability can be eliminated by disruption of the B-box 2 domain. Changes in the TRIM5αrh B-box 2 domain have been associated with alterations in TRIM5αrh turnover, the formation of cytoplasmic bodies and higher-order oligomerization. We present here the nuclear magnetic resonance structure of the TRIM5 B-box 2 domain and identify an unusual hydrophobic patch (cluster 1) on the domain surface. Alteration of cluster 1 or the flanking arginine 121 resulted in various degrees of inactivation of HIV-1 restriction, in some cases depending on compensatory changes in other nearby charged residues. For this panel of TRIM5αrh B-box 2 mutants, inhibition of HIV-1 infection was strongly correlated with higher-order self-association and binding affinity for capsid complexes but not with TRIM5αrh half-life or the formation of cytoplasmic bodies. Thus, promoting cooperative TRIM5αrh interactions with the HIV-1 capsid represents a major mechanism whereby the B-box 2 domain potentiates HIV-1 restriction.

scholarly journals Higher order assembly of Sorting Nexin 16 controls tubulation and distribution of neuronal endosomes

2018 ◽  
Author(s):  
ShiYu Wang ◽  
Zechuan Zhao ◽  
Avital A. Rodal
Keyword(s):  
Cell Body ◽  
Motor Neurons ◽  
Coiled Coil ◽  
Higher Order ◽  
Synaptic Growth ◽  
Sorting Nexin ◽  
Bmp Receptors ◽  
Self Association ◽  
Signaling Receptors

AbstractThe activities of neuronal signaling receptors depend on the maturation state of the endosomal compartments in which they reside. However, it remains unclear how the distribution of these compartments within the uniquely complex morphology of neurons is regulated, and how this distribution itself affects signaling. Here we identified mechanisms by which Sorting Nexin 16 (SNX16) controls neuronal endosomal maturation and distribution. We found that higher-order assembly of SNX16 via its coiled-coil domain drives membrane tubulation in vitro and endosome association in cells. In Drosophila motor neurons, activation of Rab5 and coiled-coil-dependent self-association of SNX16 lead to its endosomal enrichment, concomitant with depletion of SNX16-positive endosomes from the synapse, and their accumulation as Rab5- and Rab7-positive tubulated compartments at the cell body. This leads to higher levels of synaptic growth-promoting BMP receptors at the cell body, and correlates with increased synaptic growth. Our results indicate that Rab regulation of SNX16 assembly controls the endosomal distribution and signaling activities of neuronal receptors.

scholarly journals Structure of the tripartite motif of KAP1/TRIM28 identifies molecular interfaces required for transcriptional silencing of retrotransposons

2018 ◽  
Author(s):  
Guido A. Stoll ◽  
Shun-ichiro Oda ◽  
Zheng-Shan Chong ◽  
Minmin Yu ◽  
Stephen H. McLaughlin ◽  
...  
Keyword(s):  
Self Assembly ◽  
Coiled Coil ◽  
Transcriptional Silencing ◽  
Higher Order ◽  
Significant Loss ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Krab Domain ◽  
Tripartite Motif ◽  
Self Association

AbstractTranscription of transposable elements is tightly regulated to prevent damage to the genome. The family of KRAB domain-containing zinc finger proteins (KRAB-ZFPs) and KRAB-associated protein 1 (KAP1/TRIM28) play a key role in regulating retrotransposons. KRAB-ZFPs recognize specific retrotransposon sequences and recruit KAP1, which controls the assembly of an epigenetic silencing complex including histone H3K9 methyltransferase SETDB1. The chromatin remodeling activities of this complex repress transcription of the targeted transposable element and any adjacent genes. Here, we use biophysical and structural approaches to show that the tripartite motif (TRIM) of KAP1 forms antiparallel dimers, which further assemble into tetramers and higher-order oligomers in a concentration-dependent manner. Structure-based mutations in the B-box 1 domain prevented higher-order oligomerization without a significant loss of retrotransposon silencing activity in a cell-based assay, indicating that, in contrast to other TRIM family members, self-assembly is not essential for the function of KAP1. The crystal structure of the KAP1 RBCC dimer identifies the KRAB domain binding site, in the coiled-coil domain near the dyad. Mutations at this site abolished KRAB binding and transcriptional silencing activity of KAP1. This work identifies the interaction interfaces in the KAP1 RBCC motif responsible for self-association and KRAB binding and establishes their role in retrotransposon silencing.

The SPI2-encoded SseA chaperone has discrete domains required for SseB stabilization and export, and binds within the C-terminus of SseB and SseD

Microbiology ◽  
2004 ◽  
Vol 150 (7) ◽  
pp. 2055-2068 ◽  
Author(s):  
Daniel V. Zurawski ◽  
Murry A. Stein
Keyword(s):  
Type Iii Secretion ◽  
Coiled Coil ◽  
Amphipathic Helix ◽  
Yeast Two Hybrid ◽  
C Terminus ◽  
N Terminus ◽  
Domain Mapping ◽  
Self Association ◽  
Discrete Domains ◽  
Two Hybrid

SseA, a key Salmonella virulence determinant, is a small, basic pI protein encoded within the Salmonella pathogenicity island 2 and serves as a type III secretion system chaperone for SseB and SseD. Both SseA partners are subunits of the surface-localized translocon module that delivers effectors into the host cell; SseB is predicted to compose the translocon sheath and SseD is a putative translocon pore subunit. In this study, SseA molecular interactions with its partners were characterized further. Yeast two-hybrid screens indicate that SseA binding requires a C-terminal domain within both partners. An additional central domain within SseD was found to influence binding. The SseA-binding region within SseB was found to encompass a predicted amphipathic helix of a type participating in coiled-coil interactions that are implicated in the assembly of translocon sheaths. Deletions that impinge upon this putative coiled-coiled domain prevent SseA binding, suggesting that SseA occupies a portion of the coiled-coil. SseA occupancy of this motif is envisioned to be sufficient to prevent premature SseB self-association inside bacteria. Domain mapping on the chaperone was also performed. A deletion of the SseA N-terminus, or site-directed mutations within this region, allowed stabilization of SseB, but its export was disrupted. Therefore, the N-terminus of SseA provides a function that is essential for SseB export, but dispensable for partner binding and stabilization.

scholarly journals Novel TRIM5 Isoforms Expressed by Macaca nemestrina

2007 ◽  
Vol 81 (22) ◽  
pp. 12210-12217 ◽  
Author(s):  
Greg Brennan ◽  
Yury Kozyrev ◽  
Toshiaki Kodama ◽  
Shiu-Lok Hu
Keyword(s):  
Coiled Coil ◽  
Macaca Nemestrina ◽  
Cdna Clones ◽  
Reading Frame ◽  
Spry Domain ◽  
Immunodeficiency Virus ◽  
Hiv Type 1 ◽  
Hiv 1

ABSTRACT The TRIM5 family of proteins contains a RING domain, one or two B boxes, and a coiled-coil domain. The TRIM5α isoform also encodes a C-terminal B30.2(SPRY) domain, differences within which define the breadth and potency of TRIM5α-mediated retroviral restriction. Because Macaca nemestrina animals are susceptible to some human immunodeficiency virus (HIV) isolates, we sought to determine if differences exist in the TRIM5 gene and transcripts of these animals. We identified a two-nucleotide deletion (Δ2) in the transcript at the 5′ terminus of exon 7 in all M. nemestrina TRIM5 cDNA clones examined. This frameshift results in a truncated protein of 300 amino acids lacking the B30.2(SPRY) domain, which we have named TRIM5θ. This deletion is likely due to a single nucleotide polymorphism that alters the 3′ splice site between intron 6 and exon 7. In some clones, a deletion of the entire 27-nucleotide exon 7 (Δexon7) resulted in the restoration of the TRIM5 open reading frame and the generation of another novel isoform, TRIM5η. There are 18 amino acid differences between M. nemestrina TRIM5η and Macaca mulatta TRIM5α, some of which are at or near locations previously shown to affect the breadth and potency of TRIM5α-mediated restriction. Infectivity assays performed on permissive CrFK cells stably transduced with TRIM5η or TRIM5θ show that these isoforms are incapable of restricting either HIV type 1 (HIV-1) or simian immunodeficiency virus infection. The expression of TRIM5 alleles incapable of restricting HIV-1 infection may contribute to the previously reported increased susceptibility of M. nemestrina to HIV-1 infection in vivo.

scholarly journals The self-association coiled-coil domain of PML is sufficient for the oncogenic conversion of the retinoic acid receptor (RAR) alpha

Leukemia ◽  
2011 ◽  
Vol 25 (5) ◽  
pp. 814-820 ◽  
Author(s):  
M Occhionorelli ◽  
F Santoro ◽  
I Pallavicini ◽  
A Gruszka ◽  
S Moretti ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Coiled Coil ◽  
The Self ◽  
Acid Receptor ◽  
Coiled Coil Domain ◽  
Self Association

scholarly journals Tetramerization Is a Conserved Feature of the Virion-Associated Protein in Plant Pararetroviruses

2001 ◽  
Vol 75 (16) ◽  
pp. 7739-7743 ◽  
Author(s):  
Livia Stavolone ◽  
Etienne Herzog ◽  
Denis Leclerc ◽  
Thomas Hohn
Keyword(s):  
Common Property ◽  
Coiled Coil ◽  
Cauliflower Mosaic Virus ◽  
Molecular Characteristics ◽  
Yeast Two Hybrid System ◽  
Coil Structure ◽  
Self Association ◽  
Host Infection ◽  
The Many ◽  
Chemical Cross Linking

ABSTRACT All plant pararetroviruses belong to the Caulimoviridaefamily. This family contains six genera of viruses with different biological, serological, and molecular characteristics. Although some important mechanisms of viral replication and host infection are understood, much remains to be discovered about the many functions of the viral proteins. The focus of this study, the virion-associated protein (VAP), is conserved among all members of the group and contains a coiled-coil structure that has been shown to assemble as a tetramer in the case of cauliflower mosaic virus. We have used the yeast two-hybrid system to characterize self-association of the VAPs of four distinct plant pararetroviruses, each belonging to a different genus ofCaulimoviridae. Chemical cross-linking confirmed that VAPs assemble into tetramers. Tetramerization is thus a common property of these proteins in plant pararetroviruses. The possible implications of this conserved feature for VAP function are discussed.

scholarly journals Septin ring size scaling and dynamics require the coiled-coil region of Shs1p

2012 ◽  
Vol 23 (17) ◽  
pp. 3391-3406 ◽  
Author(s):  
Rebecca A. Meseroll ◽  
Louisa Howard ◽  
Amy S. Gladfelter
Keyword(s):  
Coiled Coil ◽  
Higher Order ◽  
Membrane Curvature ◽  
Negative Regulator ◽  
Ring Size ◽  
Septin Ring ◽  
Ring Assembly ◽  
Coiled Coil Domain ◽  
C Terminus ◽  
Important Negative Regulator

Septins are conserved GTP-binding proteins that assemble into heteromeric complexes that form filaments and higher-order structures in cells. What directs filament assembly, determines the size of higher-order septin structures, and governs septin dynamics is still not well understood. We previously identified two kinases essential for septin ring assembly in the filamentous fungus Ashbya gossypii and demonstrate here that the septin Shs1p is multiphosphorylated at the C-terminus of the protein near the predicted coiled-coil domain. Expression of the nonphosphorylatable allele shs1-9A does not mimic the loss of the kinase nor does complete truncation of the Shs1p C-terminus. Surprisingly, however, loss of the C-terminus or the predicted coiled-coil domain of Shs1p generates expanded zones of septin assemblies and ectopic septin fibers, as well as aberrant cell morphology. The expanded structures form coincident with ring assembly and are heteromeric. Interestingly, while septin recruitment to convex membranes is increased, septin localization is diminished at concave membranes in these mutants. Additionally, the loss of the coiled-coil leads to increased mobility of Shs1p. These data indicate the coiled-coil of Shs1p is an important negative regulator of septin ring size and mobility, and its absence may make septin assembly sensitive to local membrane curvature.

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