@article{11e03596fce94c72a9f192006e601833,
title = "An atomic model of fimbrin binding to F-actin and its implications for filament crosslinking and regulation",
abstract = "Using a new procedure that combines electron-density correlation with biochemical information, we have fitted the crystal structure of the N- terminal actin-binding domain of human T-fimbrin to helical reconstructions of fimbrin-decorated actin filaments. The map locates the N-terminal calcium- binding domain and identifies actin-binding site residues on the two calponin-homology domains of fimbrin. Based on this map, we propose a model of a fimbrin crosslink in an actin bundle and its regulation by calcium.",
author = "D. Hanein and N. Volkmann and S. Goldsmith and Michon, {A. M.} and W. Lehman and R. Craig and D. DeRosier and S. Almo and P. Matsudaira",
note = "Funding Information: Because the CH domain plays an important and varied role in organizing many aspects of the cytoskeletal function, it is impor- tant to understand the structural basis of CH-domain binding to actin. We have adopted fimbrin as a model system to study the structure and function of the CH-domain actin interaction. Fimbrin contains an N-terminal calcium-binding domain (residues 1–100) followed by a tandem pair of ABDs (ABD1 and ABD2). Each of these ABDs contains two CH domains (CH1, CH1', CH2, and CH2' respectively). Fimbrin crosslinks actin filaments through this tandem pair of ABDs. The actin bundling activity of fimbrin is inhibited by calcium11,12, indicating the importance of the N-terminal calcium binding domain. Previously, we determined the X-ray structure of ABD1 (including residues 101–375) of human T-fimbrin13 and an electron microscopy (EM) reconstruction of a larger domain, N375 (including ABD1 and the N-terminal calcium domain) bound to actin14. Difference mapping analysis lead to a preliminary model that revealed the shape of N375 and localized it{\textquoteright}s binding interface with actin14. This model of actin-binding segments was supported by crosslinking and genetic studies15,16. In this report, we combine these structural data to provide the first atomic working model for CH-domain binding to actin and the location of the calcium-binding domain.",
year = "1998",
doi = "10.1038/1828",
language = "English (US)",
volume = "5",
pages = "787--792",
journal = "Nature Structural Biology",
issn = "1072-8368",
publisher = "Nature Publishing Group",
number = "9",
}