Structural definition of the F-actin-binding THATCH domain from HIP1R.
Huntingtin-interacting protein-1 related (HIP1R) has a crucial protein-trafficking role, mediating associations between actin and clathrin-coated structures at the plasma membrane and trans-Golgi network. Here, we characterize the F-actin-binding region of HIP1R, termed the talin-HIP1/R/Sla2p actin-tethering C-terminal homology (THATCH) domain. The 1.9-A crystal structure of the human HIP1R THATCH core reveals ... a large sequence-conserved surface patch created primarily by residues from the third and fourth helices of a unique five-helix bundle. Point mutations of seven contiguous patch residues produced significant decreases in F-actin binding. We also show that THATCH domains have a conserved C-terminal latch capable of oligomerizing the core, thereby modulating F-actin engagement. Collectively, these results establish a framework for investigating the links between endocytosis and actin dynamics mediated by THATCH domain-containing proteins.
Mesh Terms:
Actins, Amino Acid Sequence, Animals, Conserved Sequence, Crystallography, X-Ray, DNA-Binding Proteins, Humans, Models, Molecular, Molecular Sequence Data, Mutation, Protein Binding, Protein Structure, Quaternary, Protein Structure, Tertiary, Sequence Alignment, Structural Homology, Protein, Vesicular Transport Proteins
Actins, Amino Acid Sequence, Animals, Conserved Sequence, Crystallography, X-Ray, DNA-Binding Proteins, Humans, Models, Molecular, Molecular Sequence Data, Mutation, Protein Binding, Protein Structure, Quaternary, Protein Structure, Tertiary, Sequence Alignment, Structural Homology, Protein, Vesicular Transport Proteins
Nat. Struct. Mol. Biol.
Date: Feb. 01, 2006
PubMed ID: 16415883
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