Functional role of
            <scp>TRIM</scp>
            E3 ligase oligomerization and regulation of catalytic activity

Koliopoulos, Marios G.; Esposito, Diego; Christodoulou, Evangelos; Taylor, Ian A.; Rittinger, Katrin

doi:10.15252/embj.201593741

Cited by 151 publications

(252 citation statements)

References 52 publications

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“…The overall architecture of the RING1/UbcH7 interface is similar to those in other RING/E2 pairs (Brown et al., 2014, Brzovic et al., 2003, DaRosa et al., 2015, Dou et al., 2012, Koliopoulos et al., 2016, Lechtenberg et al., 2016, Li et al., 2015, Plechanovova et al., 2012, Pruneda et al., 2012, Scott et al., 2014, Xu et al., 2008, Zheng et al., 2000). UbcH7 residues from loops 4 and 7 and helix 1 and HHARI RING1 residues from both Zn 2+ loops and the central helix make canonical E2/RING interactions (Figures 3A and S1A).…”

Section: Resultsmentioning

confidence: 99%

Structural Studies of HHARI/UbcH7∼Ub Reveal Unique E2∼Ub Conformational Restriction by RBR RING1

et al. 2017

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SummaryRING-between-RING (RBR) E3s contain RING1 domains that are structurally similar yet mechanistically distinct from canonical RING domains. Both types of E3 bind E2∼ubiquitin (E2∼Ub) via their RINGs but canonical RING E3s promote closed E2∼Ub conformations required for direct Ub transfer from the E2 to substrate, while RBR RING1s promote open E2∼Ub to favor Ub transfer to the E3 active site. This different RING/E2∼Ub conformation determines its direct target, which for canonical RING E3s is typically a substrate or substrate-linked Ub, but is the E3 active-site cysteine in the case of RBR-type E3s. Here we show that a short extension of HHARI RING1, namely Zn2+-loop II, not present in any RING E3s, acts as a steric wedge to disrupt closed E2∼Ub, providing a structural explanation for the distinctive RING1-dependent conformational restriction mechanism utilized by RBR E3s.

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Section: Resultsmentioning

confidence: 99%

Structural Studies of HHARI/UbcH7∼Ub Reveal Unique E2∼Ub Conformational Restriction by RBR RING1

et al. 2017

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“…26). We did not observe a dimer of TRIM56 RING in our crystal structure, raising the possibility that SopA binding may interfere with TRIM56 RING dimerization.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple studies demonstrated that the coiled-coil of various TRIMs mediates anti-parallel dimer formation21222324. Furthermore, catalytic activity of TRIM proteins is enhanced by coiled-coil-dependent dimerization and, more recently, was shown to require RING domain dimerization for the proper activation of the E2∼Ub conjugate2526.…”

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confidence: 99%

Structural basis for the recognition and degradation of host TRIM proteins by Salmonella effector SopA

et al. 2017

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The hallmark of Salmonella Typhimurium infection is an acute intestinal inflammatory response, which is mediated through the action of secreted bacterial effector proteins. The pro-inflammatory Salmonella effector SopA is a HECT-like E3 ligase, which was previously proposed to activate host RING ligases TRIM56 and TRIM65. Here we elucidate an inhibitory mechanism of TRIM56 and TRIM65 targeting by SopA. We present the crystal structure of SopA in complex with the RING domain of human TRIM56, revealing the atomic details of their interaction and the basis for SopA selectivity towards TRIM56 and TRIM65. Structure-guided biochemical analysis shows that SopA inhibits TRIM56 E3 ligase activity by occluding the E2-interacting surface of TRIM56. We further demonstrate that SopA ubiquitinates TRIM56 and TRIM65, resulting in their proteasomal degradation during infection. Our results provide the basis for how a bacterial HECT ligase blocks host RING ligases and exemplifies the multivalent power of bacterial effectors during infection.

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“…2016). This self-association enhanced E2 activity in discharge assays, consistent with what has been shown for other dimeric E2s, namely that this RING multimer stabilizes a closed-conformation of ubiquitin-loaded E2 conjugating enzymes (Dou et al.…”

Section: Trim E3 Ligases In Immune Signalingmentioning

confidence: 99%

Ubiquitin enzymes in the regulation of immune responses

Ebner

Versteeg²,

Ikeda

2017

Critical Reviews in Biochemistry and Molecular Biology

111

123

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Ubiquitination plays a central role in the regulation of various biological functions including immune responses. Ubiquitination is induced by a cascade of enzymatic reactions by E1 ubiquitin activating enzyme, E2 ubiquitin conjugating enzyme, and E3 ubiquitin ligase, and reversed by deubiquitinases. Depending on the enzymes, specific linkage types of ubiquitin chains are generated or hydrolyzed. Because different linkage types of ubiquitin chains control the fate of the substrate, understanding the regulatory mechanisms of ubiquitin enzymes is central. In this review, we highlight the most recent knowledge of ubiquitination in the immune signaling cascades including the T cell and B cell signaling cascades as well as the TNF signaling cascade regulated by various ubiquitin enzymes. Furthermore, we highlight the TRIM ubiquitin ligase family as one of the examples of critical E3 ubiquitin ligases in the regulation of immune responses.

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Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity

Cited by 151 publications

References 52 publications

Structural Studies of HHARI/UbcH7∼Ub Reveal Unique E2∼Ub Conformational Restriction by RBR RING1

Structural Studies of HHARI/UbcH7∼Ub Reveal Unique E2∼Ub Conformational Restriction by RBR RING1

Structural basis for the recognition and degradation of host TRIM proteins by Salmonella effector SopA

Ubiquitin enzymes in the regulation of immune responses

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