Nucleotide Effects on the Structure and Dynamics of Actin.

@article{citeulike:1474673, abstract = {ATP is the primary energy source within the cell, releasing its energy via hydrolysis into ADP. Actin is an important ATPase involved in many aspects of cellular function, and the binding and hydrolysis of ATP regulates its polymerization into actin filaments as well as its interaction with a host of actin associated proteins. Here we study the dynamics of monomeric actin in ATP, ADP-Pi, and ADP states via molecular dynamics simulations. As observed in some crystal structures we see that the DNase-I loop is an alpha helix in the ADP state, but forms an unstructured coil domain in the ADP-Pi and ATP states. We also find that this secondary structure change is reversible, and by mimicking nucleotide exchange we can observe the transition between the helical and coil states. Apart from the DNase-I loop, we also see several key structural differences in the nucleotide binding cleft as well as in the hydrophobic cleft between subdomains 1 and 3 where WH2 containing proteins have been shown to interact. These differences provide a structural basis for understanding the observed differences between the various nucleotide states of actin and provide some insight into how ATP regulates the interaction of actin with itself and other proteins.}, address = {Washington University.}, author = {Zheng, Xiange and Diraviyam, Karthikeyan and Sept, David}, citeulike-article-id = {1474673}, doi = {10.1529/biophysj.107.109215}, issn = {0006-3495}, journal = {Biophys J}, keywords = {actin, fullatom, md, protein}, month = {May}, posted-at = {2008-11-07 08:20:08}, priority = {2}, title = {Nucleotide Effects on the Structure and Dynamics of Actin.}, url = {http://dx.doi.org/10.1529/biophysj.107.109215}, year = {2007} }

TY - JOUR ID - citeulike:1474673 L3 - citeulike-article-id:1474673 N2 - ATP is the primary energy source within the cell, releasing its energy via hydrolysis into ADP. Actin is an important ATPase involved in many aspects of cellular function, and the binding and hydrolysis of ATP regulates its polymerization into actin filaments as well as its interaction with a host of actin associated proteins. Here we study the dynamics of monomeric actin in ATP, ADP-Pi, and ADP states via molecular dynamics simulations. As observed in some crystal structures we see that the DNase-I loop is an alpha helix in the ADP state, but forms an unstructured coil domain in the ADP-Pi and ATP states. We also find that this secondary structure change is reversible, and by mimicking nucleotide exchange we can observe the transition between the helical and coil states. Apart from the DNase-I loop, we also see several key structural differences in the nucleotide binding cleft as well as in the hydrophobic cleft between subdomains 1 and 3 where WH2 containing proteins have been shown to interact. These differences provide a structural basis for understanding the observed differences between the various nucleotide states of actin and provide some insight into how ATP regulates the interaction of actin with itself and other proteins. JF - Biophys J SN - 0006-3495 AD - Washington University. TI - Nucleotide Effects on the Structure and Dynamics of Actin. KW - actin KW - fullatom KW - md KW - protein AU - Zheng, Xiange AU - Diraviyam, Karthikeyan AU - Sept, David PY - 2007/05/25/ UR - http://dx.doi.org/10.1529/biophysj.107.109215 ER -