Crystal structure of the actin-binding domain of alpha-actinin 1: evaluating two competing actin-binding models. 2006

Emma Borrego-Diaz, and Frederic Kerff, and Sung Haeng Lee, and François Ferron, and Yu Li, and Roberto Dominguez
Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA.

Alpha-actinin belongs to the spectrin family of actin crosslinking and bundling proteins that function as key regulators of cell motility, morphology and adhesion. The actin-binding domain (ABD) of these proteins consists of two consecutive calponin homology (CH) domains. Electron microscopy studies on ABDs appear to support two competing actin-binding models, extended and compact, whereas the crystal structures typically display a compact conformation. We have determined the 1.7A resolution structure of the ABD of alpha-actinin 1, a ubiquitously expressed isoform. The structure displays the classical compact conformation. We evaluated the two binding models by surface conservation analysis. The results show a conserved surface that spans both domains and corresponds to two previously identified actin-binding sites (ABS2 and ABS3). A third, and probably less important site, ABS1, is mostly buried in the compact conformation. However, a thorough examination of existing structures suggests a weak and semi-polar binding interface between the two CHs, leaving open the possibility of domain reorientation or opening. Our results are consistent with a two-step binding mechanism in which the ABD interacts first in the compact form observed in the structures, and then transitions toward a higher affinity state, possibly through minor rearrangement of the domains.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000185 Actinin A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. alpha-Actinin,Eu-Actinin,beta-Actinin,Eu Actinin,alpha Actinin,beta Actinin
D000199 Actins Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle. F-Actin,G-Actin,Actin,Isoactin,N-Actin,alpha-Actin,alpha-Isoactin,beta-Actin,gamma-Actin,F Actin,G Actin,N Actin,alpha Actin,alpha Isoactin,beta Actin,gamma Actin
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
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

Related Publications

Emma Borrego-Diaz, and Frederic Kerff, and Sung Haeng Lee, and François Ferron, and Yu Li, and Roberto Dominguez
April 2005, Journal of molecular biology,
Emma Borrego-Diaz, and Frederic Kerff, and Sung Haeng Lee, and François Ferron, and Yu Li, and Roberto Dominguez
February 2008, Journal of molecular biology,
Emma Borrego-Diaz, and Frederic Kerff, and Sung Haeng Lee, and François Ferron, and Yu Li, and Roberto Dominguez
February 1994, FEBS letters,
Emma Borrego-Diaz, and Frederic Kerff, and Sung Haeng Lee, and François Ferron, and Yu Li, and Roberto Dominguez
November 1993, Biophysical journal,
Emma Borrego-Diaz, and Frederic Kerff, and Sung Haeng Lee, and François Ferron, and Yu Li, and Roberto Dominguez
August 1981, Biochimica et biophysica acta,
Emma Borrego-Diaz, and Frederic Kerff, and Sung Haeng Lee, and François Ferron, and Yu Li, and Roberto Dominguez
December 1991, Journal of muscle research and cell motility,
Emma Borrego-Diaz, and Frederic Kerff, and Sung Haeng Lee, and François Ferron, and Yu Li, and Roberto Dominguez
December 1992, FEBS letters,
Emma Borrego-Diaz, and Frederic Kerff, and Sung Haeng Lee, and François Ferron, and Yu Li, and Roberto Dominguez
October 1987, Cell,
Emma Borrego-Diaz, and Frederic Kerff, and Sung Haeng Lee, and François Ferron, and Yu Li, and Roberto Dominguez
May 1998, European journal of cell biology,
Emma Borrego-Diaz, and Frederic Kerff, and Sung Haeng Lee, and François Ferron, and Yu Li, and Roberto Dominguez
March 2016, FEBS letters,
Copied contents to your clipboard!