Interactions between Ca2+ binding domains of the Na+-Ca2+ exchanger and secondary regulation. 2010

Michela Ottolia, and Debora A Nicoll, and Scott John, and Kenneth D Philipson
Departments of Physiology, Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. mottolia@mednet.ucla.edu

The Na(+)-Ca(2+) exchanger (NCX) is a plasma membrane protein particularly abundant in cardiomyocytes where it plays a prominent role in Ca(2+) extrusion. In addition to being transported, cytoplasmic Ca(2+) and Na(+) regulate NCX activity by activating and inhibiting ion transport, respectively. There are two Ca(2+) binding domains within the exchanger, CBD1 and CBD2, which have been crystallized and detailed structural information obtained. We have recently studied the roles of residues coordinating Ca(2+) in both CBD1 and CBD2. To gain further insight into NCX regulation, we investigate here the presence of possible functional interactions between the two CBDs. This study reveals the important role of CBD organization in Ca(2+) regulation of the exchanger.

UI MeSH Term Description Entries
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D016254 Mutagenesis, Insertional Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation. Gene Insertion,Insertion Mutation,Insertional Activation,Insertional Mutagenesis,Linker-Insertion Mutagenesis,Mutagenesis, Cassette,Sequence Insertion,Viral Insertional Mutagenesis,Activation, Insertional,Activations, Insertional,Cassette Mutagenesis,Gene Insertions,Insertion Mutations,Insertion, Gene,Insertion, Sequence,Insertional Activations,Insertional Mutagenesis, Viral,Insertions, Gene,Insertions, Sequence,Linker Insertion Mutagenesis,Mutagenesis, Linker-Insertion,Mutagenesis, Viral Insertional,Mutation, Insertion,Mutations, Insertion,Sequence Insertions
D017433 Protein Structure, Secondary The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which align to form BETA-SHEETS), or other types of coils. This is the first folding level of protein conformation. Secondary Protein Structure,Protein Structures, Secondary,Secondary Protein Structures,Structure, Secondary Protein,Structures, Secondary Protein
D049832 Decapodiformes A superorder of CEPHALOPODS comprised of squid, cuttlefish, and their relatives. Their distinguishing feature is the modification of their fourth pair of arms into tentacles, resulting in 10 limbs. Cuttlefish,Illex,Sepiidae,Squid,Todarodes,Cuttlefishs,Decapodiforme,Illices,Squids,Todarode
D055724 Electrophysiological Phenomena The electrical properties, characteristics of living organisms, and the processes of organisms or their parts that are involved in generating and responding to electricity. Electrophysiological Concepts,Electrophysiological Processes,Electrophysiologic Concepts,Electrophysiologic Phenomena,Electrophysiological Phenomenon,Electrophysiological Process,Concept, Electrophysiologic,Concept, Electrophysiological,Concepts, Electrophysiologic,Concepts, Electrophysiological,Electrophysiologic Concept,Electrophysiological Concept,Phenomena, Electrophysiologic,Phenomena, Electrophysiological,Phenomenon, Electrophysiological,Process, Electrophysiological,Processes, Electrophysiological
D019831 Sodium-Calcium Exchanger An electrogenic ion exchange protein that maintains a steady level of calcium by removing an amount of calcium equal to that which enters the cells. It is widely distributed in most excitable membranes, including the brain and heart. Ca(2+)-Na(+) Exchanger,Calcium-Sodium Carrier,Calcium-Sodium Exchanger,Na(+)-Ca(2+) Exchanger,Sodium-Calcium Carrier,Ca(2+)-Na(+) Antiporter,Calcium-Sodium Antiporter,Na(+)-Ca(2+) Antiporter,Sodium-Calcium Antiporter,Antiporter, Calcium-Sodium,Antiporter, Sodium-Calcium,Calcium Sodium Antiporter,Calcium Sodium Carrier,Calcium Sodium Exchanger,Carrier, Calcium-Sodium,Carrier, Sodium-Calcium,Exchanger, Calcium-Sodium,Exchanger, Sodium-Calcium,Sodium Calcium Antiporter,Sodium Calcium Carrier,Sodium Calcium Exchanger

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