Mechanism of actin filament pointed-end capping by tropomodulin

Proteins that cap the ends of the actin filament are essential regulators of cytoskeleton dynamics. Whereas several proteins cap the rapidly growing barbed end, tropomodulin (Tmod) is the only protein known to cap the slowly growing pointed end. The lack of structural information severely limits our...

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Published in:Science (American Association for the Advancement of Science) 2014-07, Vol.345 (6195), p.463-467
Main Authors: Rao, Jampani Nageswara, Madasu, Yadaiah, Dominguez, Roberto
Format: Article
Language:English
Subjects:
actin
Actin Cytoskeleton - chemistry
Actins
Actins - chemistry
Amino Acid Sequence
Animals
Biochemistry
Capping
Caps (structural)
Cellular biology
Coating
Coupling (molecular)
Crystal structure
Crystallography, X-Ray
Cytoskeleton
Electron microscopes
Filaments
Humans
Microfilaments
Molecular Sequence Data
Molecules
Monomers
Mutation
Protein Binding
Protein isoforms
Protein Structure, Secondary
Protein Structure, Tertiary
Protein subunits
Proteins
Rabbits
Titration
Tropomodulin - chemistry
Tropomodulin - genetics
tropomyosins
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description Proteins that cap the ends of the actin filament are essential regulators of cytoskeleton dynamics. Whereas several proteins cap the rapidly growing barbed end, tropomodulin (Tmod) is the only protein known to cap the slowly growing pointed end. The lack of structural information severely limits our understanding of Tmod's capping mechanism. We describe crystal structures of actin complexes with the unstructured amino-terminal and the leucine-rich repeat carboxy-terminal domains of Tmod. The structures and biochemical analysis of structure-inspired mutants showed that one Tmod molecule interacts with three actin subunits at the pointed end, while also contacting two tropomyosin molecules on each side of the filament. We found that Tmod achieves high-affinity binding through several discrete low-affinity interactions, which suggests a mechanism for controlled subunit exchange at the pointed end.
doi_str_mv 10.1126/science.1256159
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subjects actin
Actin Cytoskeleton - chemistry
Actins
Actins - chemistry
Amino Acid Sequence
Animals
Biochemistry
Capping
Caps (structural)
Cellular biology
Coating
Coupling (molecular)
Crystal structure
Crystallography, X-Ray
Cytoskeleton
Electron microscopes
Filaments
Humans
Microfilaments
Molecular Sequence Data
Molecules
Monomers
Mutation
Protein Binding
Protein isoforms
Protein Structure, Secondary
Protein Structure, Tertiary
Protein subunits
Proteins
Rabbits
Titration
Tropomodulin - chemistry
Tropomodulin - genetics
tropomyosins
title Mechanism of actin filament pointed-end capping by tropomodulin
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