The Structure of an Open State of β-Actin at 2.65 Å Resolution

Chik, John K.; Lindberg, Uno; Schutt, Clarence E.

doi:10.1006/jmbi.1996.0602

Cited by 208 publications

(273 citation statements)

References 58 publications

(74 reference statements)

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“…Profilin, a small protein that binds to the barbed-end groove of actin, 15 can stabilize an open conformation 14 and binds with higher affinity to nucleotide-free actin than ATP-actin or ADP-actin. 8 MD simulations have shown that removal of profilin from the open actin-profilin complex results in the closure of the nucleotide binding cleft of actin on nanosecond timescales.…”

Section: Structural Basis For Differences Between Actin and Arp3mentioning

confidence: 99%

“…Most relevant to this study are molecular dynamics (MD) simulations of monomeric actin up to 50 ns in explicit water, where the nucleotide binding cleft of actin stayed closed when bound to both ATP and ADP. 29 A simulation of actin-profilin showed that the open nucleotide binding cleft as observed in crystal structures 14 was unstable when profilin was replaced with water. 25 Here, we used MD simulations to study conformations of actin and Arp3 in a variety of nucleotide-bound states on the nanosecond timescale.…”

Section: Introductionmentioning

confidence: 99%

“…In most crystal structures of actin, the nucleotide binding cleft is closed around either ATP or ADP. [13][14][15][16][17][18] So far, the cleft is open only in certain crystals of ATP-β-actin bound to profilin, where the P1 and P2 loops were separated by an additional 3 Å from closed conformations. 14 However, the cleft was closed in crystals of the same complex grown in different conditions.…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15][16][17][18] So far, the cleft is open only in certain crystals of ATP-β-actin bound to profilin, where the P1 and P2 loops were separated by an additional 3 Å from closed conformations. 14 However, the cleft was closed in crystals of the same complex grown in different conditions. 15 On larger length scales, reconstructions of electron micrographs of budding yeast actin filaments show the nucleotide cleft open in ADP filaments and closed in ADP filaments in beryllium fluoride (to mimic ADP-P i ).…”

Section: Introductionmentioning

confidence: 99%

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Nucleotide-Mediated Conformational Changes of Monomeric Actin and Arp3 Studied by Molecular Dynamics Simulations

Dalhaimer

Pollard

Nolen

2008

Journal of Molecular Biology

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Members of the actin family of proteins exhibit different biochemical properties when ATP, ADP-P i , ADP, or no nucleotide is bound. We used molecular dynamics simulations to study the effect of nucleotides on the behavior of actin and actin-related protein 3 (Arp3). In all of the actin simulations, the nucleotide cleft stayed closed, as in most crystal structures. ADP was much more mobile within the cleft than ATP, despite the fact that both nucleotides adopt identical conformations in actin crystal structures. The nucleotide cleft of Arp3 opened in most simulations with ATP, ADP, and no bound nucleotide. Deletion of a C-terminal region of Arp3 that extends beyond the conserved actin sequence reduced the tendency of the Arp3 cleft to open. When the Arp3 cleft opened, we observed multiple instances of partial release of the nucleotide. Cleft opening in Arp3 also allowed us to observe correlated movements of the phosphate clamp, cleft mouth, and barbed-end groove, providing a way for changes in the nucleotide state to be relayed to other parts of Arp3. The DNase binding loop of actin was highly flexible regardless of the nucleotide state. The conformation of Ser14/Thr14 in the P1 loop was sensitive to the presence of the γ-phosphate, but other changes observed in crystal structures were not correlated with the nucleotide state on nanosecond timescales. The divalent cation occupied three positions in the nucleotide cleft, one of which was not previously observed in actin or Arp2/3 complex structures. In sum, these simulations show that subtle differences in structures of actin family proteins have profound effects on their nucleotide-driven behavior.

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Section: Structural Basis For Differences Between Actin and Arp3mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nucleotide-Mediated Conformational Changes of Monomeric Actin and Arp3 Studied by Molecular Dynamics Simulations

Dalhaimer

Pollard

Nolen

2008

Journal of Molecular Biology

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“…Chik et al (1996) demonstrated using β-actin that actin can exist in both an open and a closed state, and that the conformational changes can be much larger than a 5° hinge motion. Crystallographic studies revealed that trisoxazole macrolides , swinholide A (Klenchin et al 2005) and aplyronine A bind to G-actin (Hirata et al 2006) in a closed conformation, which explains the inhibitory effect of toxins on exchange of the nucleotide bound in G-actin .…”

Section: Sphinxolides and Reidispongiolidesmentioning

confidence: 99%

Developmental Biology of Neoplastic Growth

Macieira‐Coelho¹

2005

Progress in Molecular and Subcellular Biology

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Protein domain movements: detection of rigid domains and visualization of hinges in comparisons of atomic coordinates

1997

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The activity of many proteins induces conformational transitions by hinge-bending, which involves the movement of relatively rigid parts of a protein about flexible joints. We present an algorithm to identify and visualize the movements of rigid domains about common hinges in proteins. In comparing two structures, the method partitions a protein into domains of preserved geometry. The domains are extracted by an adaptive selection procedure using least-squares fitting. The user can maintain the spatial connectivity of the domains and filter significant structural differences (domain movements) from noise in the compared sets of atomic coordinates. The algorithm subsequently characterizes the relative movements of the found domains by effective rotation axes (hinges). The method is applied to several known instances of domain movements in protein structures, namely, in lactoferrin, hexokinase, actin, the extracellular domains of human tissue factor, and the receptor of human growth factor. The results are visualized with the molecular graphics package VMD (Humphrey et al., J. Mol. Graphics 14(1):33-38, 1996). Applications of the algorithm to the analysis of conformational changes in proteins and to biomolecular docking are discussed.

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The Structure of an Open State of β-Actin at 2.65 Å Resolution

Cited by 208 publications

References 58 publications

Nucleotide-Mediated Conformational Changes of Monomeric Actin and Arp3 Studied by Molecular Dynamics Simulations

Nucleotide-Mediated Conformational Changes of Monomeric Actin and Arp3 Studied by Molecular Dynamics Simulations

Developmental Biology of Neoplastic Growth

Protein domain movements: detection of rigid domains and visualization of hinges in comparisons of atomic coordinates

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