Structure of the Oncoprotein Gankyrin in Complex with S6 ATPase of the 26S Proteasome

Nakamura, Yoshihiro; Nakano, Kazumi; Umehara, Takashi; Kimura, Mayumi; Hayashizaki, Yoshihide; Tanaka, Akiko; Horikoshi, Masami; Padmanabhan, Balasundaram; Yokoyama, Shigeyuki

doi:10.1016/j.str.2006.11.015

Cited by 62 publications

(76 citation statements)

References 46 publications

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“…In fact, because of C-terminal proteolytic processing of a fraction of the FLAGRpt3(ϪC3) protein, we could directly discriminate between the effect of deletion of the HbYX residues and the effect of more extensive C-terminal deletions on PA700 assembly. Thus, unlike the unprocessed Rpt3(ϪC3), larger C-terminal truncations inhibited PA700 assembly per se, perhaps as a consequence of lost interactions between Rpt3 and cognate PA700 assembly chaperones, such as p28 (42). The exact reason for the lack of processing of wild-type Rpt3 compared with mutant Rpt3 is uncertain but seems unlikely to be related to an inherent structural role of the deleted residues because no processing occurred when the same mutant protein was expressed transiently (25).…”

Section: Discussionmentioning

confidence: 99%

C Termini of Proteasomal ATPases Play Nonequivalent Roles in Cellular Assembly of Mammalian 26 S Proteasome

Kim

DeMartino

2011

Journal of Biological Chemistry

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The 26 S proteasome comprises two multisubunit subcomplexes as follows: 20 S proteasome and PA700/19 S regulatory particle. The cellular mechanisms by which these subcomplexes assemble into 26 S proteasome and the molecular determinants that govern the assembly process are poorly defined. Here, we demonstrate the nonequivalent roles of the C termini of six AAA subunits (Rpt1-Rpt6) of PA700 in 26 S proteasome assembly in mammalian cells. The C-terminal HbYX motif (where Hb is a hydrophobic residue, Y is tyrosine, and X is any amino acid) of each of two subunits, Rpt3 and Rpt5, but not that of a third subunit Rpt2, was essential for assembly of 26 S proteasome. The C termini of none of the three non-HbYX motif Rpt subunits were essential for cellular 26 S proteasome assembly, although deletion of the last three residues of Rpt6 destabilized the 20 S-PA700 interaction. Rpt subunits defective for assembly into 26 S proteasome due to C-terminal truncations were incorporated into intact PA700. Moreover, intact PA700 accumulated as an isolated subcomplex when cellular 20 S proteasome content was reduced by RNAi. These results indicate that 20 S proteasome is not an obligatory template for assembly of PA700. Collectively, these results identify specific structural elements of two Rpt subunits required for 26 S proteasome assembly, demonstrate that PA700 can be assembled independently of the 20 S proteasome, and suggest that intact PA700 is a direct intermediate in the cellular pathway of 26 S proteasome assembly.

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Section: Discussionmentioning

confidence: 99%

C Termini of Proteasomal ATPases Play Nonequivalent Roles in Cellular Assembly of Mammalian 26 S Proteasome

Kim

DeMartino

2011

Journal of Biological Chemistry

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“…(A) Structure of Gankyrin bound to the S6 ATPase of the 26S proteasome (grey). 48 (B) Structure of the ankyrin repeats of RNase L bound to an oligoadenylate trimer (spheres). 20 (C) Structure of the ankyrin repeats of TRPV1 bound to ATP (spheres).…”

Section: Discussionmentioning

confidence: 99%

A primer on ankyrin repeat function in TRP channels and beyond

2008

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Transient Receptor Potential (TRP) channels are rapidly gaining attention as important receptors and transducers of diverse sensory and environmental cues. Recent progress in the field has provided new insights into the structure and function of the ankyrin repeat motifs present in the Nterminal cytosolic domain of many TRP channels. The topics addressed in this review include the structural features of canonical ankyrin repeats, new clues into the functions these repeats perform in cells, and how this information can be applied to develop further experiments on TRP channels and other proteins containing ankyrin repeats.TRP proteins form a large family of ion channels particularly important in animals from worms to man, with more than 30 members in mammals. 1 The founding family member, the Drosophila trp gene -named for the "transient receptor potential" phenotype its mutation causes in light perception by photoreceptors -was first cloned in 1989. 2 The functions assigned to TRP channels in physiology are constantly expanding. They are key transducers of sensory signals, and are generally important in sensing information about the environment in both neuronal and non-neuronal cells (see ref. 3 for comprehensive reviews). Some TRP channels are found in excitable cells of the sensory nervous system, while others are expressed in various other tissues and organs. TRP channels have been implicated in many physiological processes, including calcium and magnesium homeostasis, neuronal growth, temperature sensation and pain perception, to name a few. For example, TRPV1 senses painfully hot temperatures, low extracellular pH and the capsaicin of "hot" chili peppers, while TRPA1 senses many painful chemical stimuli, including the pungent compounds in wasabi and cinnamon. TRPV1 and TRPA1 are expressed in partially overlapping sets of nociceptor neurons that transmit pain signals to the brain.At a molecular level, TRP channels assemble as tetramers through a channel domain that spans the membrane six times and has sequence similarity to voltage-gated ion channels. TRP channels also have large N-and C-terminal cytosolic domains that flank the transmembrane channel domain. These cytosolic domains participate in channel gating and regulation and sense information about the cellular state -ion and metabolite levels, for example. The TRP channel family is divided into seven subfamilies based on sequence similarity 1 : TRPA (ankyrin), TRPC (canonical), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), TRPV (vanilloid), and TRPN (NOMPC). Several of these subfamilies -TRPA, TRPC, TRPN and TRPV -have ankyrin repeat sequence motifs in their N-terminal cytosolic domains. Recent work from my lab and others has taken a structural biology approach to elucidate the roles of these ankyrin repeats in TRP channel function. [4][5][6][7][8][9] The emerging structural and functional features of these TRP channel ankyrin repeats are the focus of this short review. NIH Public Access Ankyrin repeats and their structureAnkyrin rep...

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“…The C-terminal domain of S6 (S6-C) binds to Gankyrin across the concave surface formed by the ␤-hairpin turns of all seven ankyrin repeats, forming a stable complex and thus constraining Gankyrin in a rigid ankyrin fold (40). We co-purified Trx-6H-S6-C bound to GST-tagged Gankyrin via Ni 2ϩ affinity chromatography.…”

Section: Resultsmentioning

confidence: 99%

Factor Inhibiting HIF (FIH) Recognizes Distinct Molecular Features within Hypoxia-inducible Factor-α (HIF-α) versus Ankyrin Repeat Substrates

Wilkins

Karttunen

Hampton‐Smith

et al. 2012

Journal of Biological Chemistry

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Background:The oxygen-dependent asparaginyl hydroxylase FIH has two classes of substrate, HIF and ARD proteins. Results: Substrate recognition by FIH is mediated by structural context and specific amino acids proximal and distal to the target asparagine. Conclusion: Differences in sequence and structure explain distinct kinetic properties of HIF and ARD substrates.Significance: These data demonstrate how FIH substrate selection can be achieved in vivo.

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Structure of the Oncoprotein Gankyrin in Complex with S6 ATPase of the 26S Proteasome

Cited by 62 publications

References 46 publications

C Termini of Proteasomal ATPases Play Nonequivalent Roles in Cellular Assembly of Mammalian 26 S Proteasome

C Termini of Proteasomal ATPases Play Nonequivalent Roles in Cellular Assembly of Mammalian 26 S Proteasome

A primer on ankyrin repeat function in TRP channels and beyond

Factor Inhibiting HIF (FIH) Recognizes Distinct Molecular Features within Hypoxia-inducible Factor-α (HIF-α) versus Ankyrin Repeat Substrates

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