Reinterpreting the Action of ATP Analogs on KATP Channels

Ortiz, David; Gossack, Lindsay; Quast, Ulrich; Bryan, Joseph

doi:10.1074/jbc.m113.476887

Cited by 29 publications

(44 citation statements)

References 58 publications

(58 reference statements)

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“…Fap7•AMPPCP provides intermediate level of protection. Similar compromised activity from the non-hydrolyzable ATP analog has been observed in other systems (Ortiz et al, 2013; Yount et al, 1971). Together, these data strongly suggest that 80S-like ribosomes are in the classic conformation, and that addition of Fap7•ATP promotes formation of the rotated state.…”

Section: Resultssupporting

confidence: 81%

The ATPase Fap7 Tests the Ability to Carry Out Translocation-like Conformational Changes and Releases Dim1 during 40S Ribosome Maturation

et al. 2017

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SUMMARY Late in their maturation, nascent small (40S) ribosomal subunits bind 60S subunits to produce 80S-like ribosomes. Due to the analogy of this translation-like cycle to actual translation, and because 80S-like ribosomes do not produce any protein, it was suggested that this represents a quality-control mechanism for subunit functionality. Here, we use genetic and biochemical experiments to show that the essential ATPase Fap7 promotes formation of the rotated state, a key intermediate in translocation, thereby releasing the essential assembly factor Dim1 from pre-40S subunits. Bypassing this quality control step produces defects in reading frame maintenance. These results show how progress in the maturation cascade is linked to a test for a key functionality of 40S ribosomes, their ability to translocate the mRNA•tRNA pair. Furthermore, our data demonstrate for the first time that the translation-like cycle is a quality control mechanism that ensures the fidelity of the cellular ribosome pool.

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Section: Resultssupporting

confidence: 81%

The ATPase Fap7 Tests the Ability to Carry Out Translocation-like Conformational Changes and Releases Dim1 during 40S Ribosome Maturation

et al. 2017

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“…Studies on CFTR and SUR1 revealed that AMP-PNP is a poor ATP analog in heterodimeric ABC exporters. For CFTR, a 20-fold decreased opening rate was observed for AMP-PNP compared with ATP (31) and in SUR1, AMP-PNP fails to support NBD dimerization and conformational switching (32).…”

Section: Discussionmentioning

confidence: 99%

Structural basis for allosteric cross-talk between the asymmetric nucleotide binding sites of a heterodimeric ABC exporter

Höhl

Hürlimann

Böhm

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

109

153

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ATP binding cassette (ABC) transporters mediate vital transport processes in every living cell. ATP hydrolysis, which fuels transport, displays positive cooperativity in numerous ABC transporters. In particular, heterodimeric ABC exporters exhibit pronounced allosteric coupling between a catalytically impaired degenerate site, where nucleotides bind tightly, and a consensus site, at which ATP is hydrolyzed in every transport cycle. Whereas the functional phenomenon of cooperativity is well described, its structural basis remains poorly understood. Here, we present the apo structure of the heterodimeric ABC exporter TM287/288 and compare it to the previously solved structure with adenosine 5′-(β,γ-imido)triphosphate (AMP-PNP) bound at the degenerate site. In contrast to other ABC exporter structures, the nucleotide binding domains (NBDs) of TM287/288 remain in molecular contact even in the absence of nucleotides, and the arrangement of the transmembrane domains (TMDs) is not influenced by AMP-PNP binding, a notion confirmed by double electron-electron resonance (DEER) measurements. Nucleotide binding at the degenerate site results in structural rearrangements, which are transmitted to the consensus site via two D-loops located at the NBD interface. These loops owe their name from a highly conserved aspartate and are directly connected to the catalytically important Walker B motif. The D-loop at the degenerate site ties the NBDs together even in the absence of nucleotides and substitution of its aspartate by alanine is well-tolerated. By contrast, the D-loop of the consensus site is flexible and the aspartate to alanine mutation and conformational restriction by cross-linking strongly reduces ATP hydrolysis and substrate transport.membrane transport | X-ray crystallography | allosteric communication A BC exporters are found in every organism (1, 2). They minimally consist of four domains and exist as homodimers or heterodimers. Two transmembrane domains (TMDs) span the membrane with a total of 12 transmembrane helices and form the substrate permeation pathway by alternating between inward-and outward-oriented states (Fig. S1A). A pair of nucleotide binding domains (NBDs) is connected to the TMDs via coupling helices and drive conformational cycling of the transporter by binding and hydrolysis of ATP, a process which is linked to NBD dimerization and dissociation (3).In their closed state, the NBDs sandwich two ATP molecules at the dimer interface by composite ATP binding sites involving conserved sequence motifs contributed by both subunits (4, 5). The A-loop and Walker A motif of one NBD and the ABC signature motif of the opposite NBD are involved in nucleotide binding. The Walker B glutamate and the switch-loop histidine constitute a catalytic dyad required for ATP hydrolysis (6, 7). In heterodimeric ABC exporters with asymmetric ATP binding sites, these catalytic residues are noncanonical at the degenerate site and ATP is therefore primarily, if not exclusively, hydrolyzed at the consensus site (8). The Q-and D...

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“…Chemical shift mapping also indicates that transient interactions occur with NBD1 residues that bind NBD2. Phosphorylation promotes stabilization of NBD1 into a conformation that allows NBD1 to make productive interactions (80), such as with MgATP and/or NBD2, leading to increased K ATP channel opening (12). Thus, the model (Fig.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation-dependent Changes in Nucleotide Binding, Conformation, and Dynamics of the First Nucleotide Binding Domain (NBD1) of the Sulfonylurea Receptor 2B (SUR2B)

Araujo

Alvarez

López‐Alonso

et al. 2015

Journal of Biological Chemistry

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Reinterpreting the Action of ATP Analogs on KATP Channels

Cited by 29 publications

References 58 publications

The ATPase Fap7 Tests the Ability to Carry Out Translocation-like Conformational Changes and Releases Dim1 during 40S Ribosome Maturation

The ATPase Fap7 Tests the Ability to Carry Out Translocation-like Conformational Changes and Releases Dim1 during 40S Ribosome Maturation

Structural basis for allosteric cross-talk between the asymmetric nucleotide binding sites of a heterodimeric ABC exporter

Phosphorylation-dependent Changes in Nucleotide Binding, Conformation, and Dynamics of the First Nucleotide Binding Domain (NBD1) of the Sulfonylurea Receptor 2B (SUR2B)

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