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Title: Electrostatic interactions between the Bni1p formin FH2 domain and actin influence actin filament nucleation

Formins catalyze nucleation and growth of actin filaments. In this paper, we study the structure and interactions of actin with the FH2 domain of budding yeast formin Bni1p. We built an all-atom model of the formin dimer on an Oda actin filament 7-mer and studied structural relaxation and interprotein interactions by molecular dynamics simulations. These simulations produced a refined model for the FH2 dimer associated with the barbed end of the filament and showed electrostatic interactions between the formin knob and actin target-binding cleft. Mutations of two formin residues contributing to these interactions (R1423N, K1467L, or both) reduced the interaction energies between the proteins, and in coarse-grained simulations, the formin lost more interprotein contacts with an actin dimer than with an actin 7-mer. Finally, biochemical experiments confirmed a strong influence of these mutations on Bni1p-mediated actin filament nucleation, but not elongation, suggesting that different interactions contribute to these two functions of formins.
Authors:
 [1] ;  [2] ;  [3] ;  [1] ;  [2] ;  [1]
  1. The Univ. of Chicago, Chicago, IL (United States)
  2. Yale Univ., New Haven, CT (United States)
  3. Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
Publication Date:
OSTI Identifier:
1242545
Grant/Contract Number:
AC02-06CH11357
Type:
Published Article
Journal Name:
Structure
Additional Journal Information:
Journal Volume: 23; Journal Issue: 1; Journal ID: ISSN 0969-2126
Publisher:
Elsevier
Research Org:
Univ. of Chicago, IL (United States)
Sponsoring Org:
USDOE Office of Science (SC)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES