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Presents information on a study which introduced an approach to making the nuclear magnetic resonance (NMR) relaxation properties of large proteins amenable to modern solution NMR techniques. Other approaches that have been developed to combat the limitations caused by relaxation times (T2); Materials and methods; Results and discussion.

Studies the interaction of apocalmodulin with a peptide based on the primary sequence of the calmodulin-binding domain of neuromodulin. Fluorescence spectroscopy; Fluorescence emission and anistropy measurements; Effect of ionic strength and hydrostatic pressure on acceptor enhancement fluorescence-energy transfer experiments.

Presents a study of the structural dynamics and energetics of the interaction of a peptide. Calmodulin binding domain of the smooth muscle myosin light chain kinase with calcium-saturated calmodulin; Potential of hydrogen exchange for studying the dynamics and energetics of interprotein interactions along free energy path.

The ATR (ATM and Rad3-related) kinase is essential to maintain genomic integrity. ATR is recruited to DNA lesions in part through its association with ATR-interacting protein (ATRIP), which in turn interacts with the single-stranded DNA binding protein RPA (replication protein A). In this study, a conserved checkpoint protein recruitment domain (CRD) in ATRIP orthologs was identified by biochemical mapping of the RPA binding site in combination with nuclear magnetic resonance, mutagenesis, and computational modeling. Mutations in the CRD of the Saccharomyces cerevisiae ATRIP ortholog Ddc2 disrupt the Ddc2-RPA interaction, prevent proper localization of Ddc2 to DNA breaks, sensitize yeast to DNA-damaging agents, and partially compromise checkpoint signaling. These data demonstrate that the CRD is critical for localization and optimal DNA damage responses. However, the stimulation of ATR kinase activity by binding of topoisomerase binding protein 1 (TopBP1) to ATRIP-ATR can occur independently of the interaction of ATRIP with RPA. Our results support the idea of a multistep model for ATR activation that requires separable localization and activation functions of ATRIP. [ABSTRACT FROM AUTHOR]