X-Ray Structure of RLI, an Essential Twin Cassette ABC ATPase Involved in Ribosome Biogenesis and HIV Capsid Assembly

Karcher, Annette; ̈ttner, Katharina Bu; Märtens, Birgit; Jansen, Ralf‐Peter; Hopfner, Karl‐Peter

doi:10.1016/j.str.2005.02.008

Cited by 68 publications

(78 citation statements)

References 50 publications

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“…This can be observed in two structures of the DNA mismatch repair enzyme MutS (Lamers et al 2000;Obmolova et al 2000) as well as in the structure of the RNase-L inhibitor, a key enzyme in ribosome biogenesis, formation of translation preinitiation complexes and assembly of HIV capsids (Karcher et al 2005).…”

Section: Conformation Of the Monomermentioning

confidence: 95%

The motor domains of ABC-transporters

Oswald

Holland

Schmitt

2006

Naunyn Schmied Arch Pharmacol

133

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The transport of substrates across a cellular membrane is a vitally important biological function essential for cell survival. ATP-binding cassette (ABC) transporters constitute one of the largest subfamilies of membrane proteins, accomplishing this task. Mutations in genes encoding for ABC transporters cause different diseases, for example, Adrenoleukodystrophy, Stargardt disease or Cystic Fibrosis. Furthermore, some ABC transporters are responsible for multidrug resistance, presenting a major obstacle in modern cancer chemotherapy. In order to translocate the enormous variety of substrates, ranging from ions, nutrients, small peptides to large toxins, different ABC-transporters utilize the energy gained from ATP binding and hydrolysis. The ATP binding cassette, also called the motor domain of ABC transporters, is highly conserved among all ABC transporters. The ability to purify this domain rather easily presents a perfect possibility to investigate the mechanism of ATP hydrolysis, thus providing us with a detailed picture of this process. Recently, many crystal structures of the ATP-binding domain and the full-length structures of two ABC transporters have been solved. Combining these structural data, we have now the opportunity to analyze the hydrolysis event on a molecular level. This review provides an overview of the structural investigations of the ATPbinding domains, highlighting molecular changes upon ATP binding and hydrolysis.

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Section: Conformation Of the Monomermentioning

confidence: 95%

The motor domains of ABC-transporters

Oswald

Holland

Schmitt

2006

Naunyn Schmied Arch Pharmacol

133

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“…Docking of X-ray structures and molecular models of eEF3 42,43 and ribosomal proteins/RNA 44 was done with IRIS Explorer, SPIDER 41 , O 32 and ERNA-3D 45 . Using the program Situs 46 for docking of MalK-based 47 ATP and ADP models for A conformational switch of the chromodomain stabilizes the L1 stalk in the 'out' position (unlocked E).…”

Section: Methodsmentioning

confidence: 99%

Structure of eEF3 and the mechanism of transfer RNA release from the E-site

Andersen

Becker

Blau

et al. 2006

Nature

152

166

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Elongation factor eEF3 is an ATPase that, in addition to the two canonical factors eEF1A and eEF2, serves an essential function in the translation cycle of fungi. eEF3 is required for the binding of the aminoacyl-tRNA-eEF1A-GTP ternary complex to the ribosomal A-site and has been suggested to facilitate the clearance of deacyl-tRNA from the E-site. Here we present the crystal structure of Saccharomyces cerevisiae eEF3, showing that it consists of an amino-terminal HEAT repeat domain, followed by a four-helix bundle and two ABC-type ATPase domains, with a chromodomain inserted in ABC2. Moreover, we present the cryo-electron microscopy structure of the ATP-bound form of eEF3 in complex with the post-translocational-state 80S ribosome from yeast. eEF3 uses an entirely new factor binding site near the ribosomal E-site, with the chromodomain likely to stabilize the ribosomal L1 stalk in an open conformation, thus allowing tRNA release.Protein synthesis requires, in general, only two canonical GTPase elongation factors. eEF1A (known as EF-Tu in prokaryotes) recruits cognate aminoacyl-tRNAs to the A-site of the ribosome, and, after peptidyl transfer, eEF2 (EF-G in prokaryotes) catalyses translocation of the messenger RNA and the transfer RNAs from the A-and P-sites to the P-and E-sites. In contrast to the canonical factors, eEF3 has an ATPase activity that is stimulated by ribosomes. It interacts with both ribosomal subunits 1-3 , competes with eEF2 for binding to ribosomes, and stimulates eEF1A-dependent binding of cognate aminoacyltRNA to the ribosomal A-site 1,4 . Because, according to the allosteric three-site model of the ribosomal elongation cycle, E-site release is required for efficient A-site binding, it has been suggested that eEF3 functions as a so-called 'E-site factor' 4,5 . Moreover, ATP hydrolysis by eEF3 is required in every elongation cycle to allow chasing of deacyltRNA from the E-site 4 .eEF3 belongs to the family of ABC (ATP-binding cassette) proteins that includes proteins involved in transport across membranes, DNA repair, and translation. The membrane proteins of this class especially represent important targets for development of novel therapeutic strategies. The proteins contain ATP/ADP-binding ABC domains, which convert chemical energy derived from binding of ATP or its hydrolysis into a 'powerstroke' of mechanical energy 6 . ABC proteins function as either homodimers or as twin-cassette proteins with two ABC domains within the same polypeptide.The ribosome exhibits very dynamic behaviour, such as the ratchet movement 7 or the movement of the L1 and the L7/L12 stalks [8][9][10][11] . Hence, an intriguing question is how the interaction of eEF3 with the ribosome is correlated with its dynamic properties as an ABC protein, and how the energy derived from binding/hydrolysis of ATP is used for its function. Crystal structure of eEF3Three crystal structures of residues 1-980 of eEF3 in the apo state (2.7 Å ), in complex with ADP (2.4 Å ), or in complex with the nonhydrolysable ATP analogue ADPNP (3...

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“…Remarkably, ADP was retained at the protein from the cells throughout purification and could not be exchanged to ATP or non-hydrolysable derivatives in our hands. Related structures form other organisms from ourselves and others revealed a similar ADP-state and even mutating the Walker B motif to prevent ATP hydrolysis still resulted in ADP-bound active sites (Karcher et al , 2005 ;Karcher et al , 2008 ;Barthelme et al , 2011 ). Unfolding followed by refolding of the protein in the presence of AMP-PNP removed ADP in favor of AMP-PNP, but rather than a structural change in the protein, AMP-PNP was forced to adopt an unusual ADP-like conformation with misplaced γ -phosphate (unpublished).…”

Section: Structure Of Abce1mentioning

confidence: 74%

“…At the same time, the Lill and Hurt labs found a functional link between the iron-sulfur clusters of ABCE1 and ribosome biogenesis (Kispal et al , 2005 ;Yarunin et al , 2005 ) while we could crystallize and determine the crystal structure of the twin ABC cassette of archaeal ABCE1 bound to ADP (Karcher et al , 2005 ) ( Figure 2). Studies in flies then showed that ABCE1 (known as Pixie in Drosophila) binds the 40S ribosome in an ATPdependent manner and depletion leads to an increase in in empty 80S ribosomes (Andersen and Leevers , 2007 ).…”

Section: Abc Enzymes: Versatile Molecular Machines or Switchesmentioning

confidence: 96%

“…The phylogenetic distribution suggested that ABCE1 is involved in a rather fundamental process in life that is conserved in archaea and eukaryotes, but mechanistically distinct in bacteria. In support of a core role in eukaryotic and archaeal cell physiology, ABCE1 turned out to be essential in all organisms tested (Dong et al , 2004 ;Zhao et al , 2004 ;Coelho et al , 2005 ;Karcher et al , 2005 ;Kispal et al , 2005 ;Yarunin et al , 2005 ).…”

Section: Abc Enzymes: Versatile Molecular Machines or Switchesmentioning

confidence: 98%

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Rustless translation

Hopfner

2012

Biological Chemistry

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: ATP binding cassette proteins are a large and diverse family of molecular machines and include transmembrane transporter, chromosome maintenance and DNA repair proteins, and translation factors. However, the function of the ABCE1, the only member of subfamily E of ABC proteins, remained mysterious for over a decade, even though it is perhaps the most conserved ABC protein in eukaryotes and archaea. Recent results have now identified ABCE1 as the ribosome-recycling factor of eukaryotes and archaea. Thus, two iron-sulfur clustersthe hallmark feature of ABCE1 -help catalyze an integral step of the translational cycle at the core of the protein synthesis machinery.

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X-Ray Structure of RLI, an Essential Twin Cassette ABC ATPase Involved in Ribosome Biogenesis and HIV Capsid Assembly

Cited by 68 publications

References 50 publications

The motor domains of ABC-transporters

The motor domains of ABC-transporters

Structure of eEF3 and the mechanism of transfer RNA release from the E-site

Rustless translation

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