Control of the Ability of Profilin to Bind and Facilitate Nucleotide Exchange from G-actin

Kuo-Kuang Wen; Melissa McKane; Jon C. D Houtman; Peter A Rubenstein

doi:10.1074/jbc.M709806200

Back

Control of the Ability of Profilin to Bind and Facilitate Nucleotide Exchange from G-actin

Journal article

Open access

Peer reviewed

Control of the Ability of Profilin to Bind and Facilitate Nucleotide Exchange from G-actin

Kuo-Kuang Wen, Melissa McKane, Jon C. D Houtman and Peter A Rubenstein

The Journal of biological chemistry, Vol.283(14), pp.9444-9453

04/04/2008

DOI: 10.1074/jbc.M709806200

PMCID: PMC2431015

PMID: 18223293

Files and links (1)

url

https://doi.org/10.1074/jbc.M709806200View

Published (Version of record) Open Access

Abstract

A major factor in profilin regulation of actin cytoskeletal dynamics is its facilitation of G-actin nucleotide exchange. However, the mechanism of this facilitation is unknown. We studied the interaction of yeast (YPF) and human profilin 1 (HPF1) with yeast and mammalian skeletal muscle actins. Homologous pairs (YPF and yeast actin, HPF1 and muscle actin) bound more tightly to one another than heterologous pairs. However, with saturating profilin, HPF1 caused a faster etheno-ATP exchange with both yeast and muscle actins than did YPF. Based on the -fold change in ATP exchange rate/ K d , however, the homologous pairs are more efficient than the heterologous pairs. Thus, strength of binding of profilin to actin and nucleotide exchange rate are not tightly coupled. Actin/HPF interactions were entropically driven, whereas YPF interactions were enthalpically driven. Hybrid yeast actins containing subdomain 1 (sub1) or subdomain 1 and 2 (sub12) muscle actin residues bound more weakly to YPF than did yeast actin ( K d = 2 μ m versus 0.6 μ m ). These hybrids bound even more weakly to HPF than did yeast actin ( K d = 5 μ m versus 3.2 μ m ). sub1/YPF interactions were entropically driven, whereas the sub12/YPF binding was enthalpically driven. Compared with WT yeast actin, YPF binding to sub1 occurred with a 5 times faster k off and a 2 times faster k on . sub12 bound with a 3 times faster k off and a 1.5 times slower k on . Profilin controls the energetics of its interaction with nonhybrid actin, but interactions between actin subdomains 1 and 2 affect the topography of the profilin binding site.

Enzyme Catalysis and Regulation

Details

Title: Subtitle: Control of the Ability of Profilin to Bind and Facilitate Nucleotide Exchange from G-actin
Creators: Kuo-Kuang Wen - Departments of
Melissa McKane - Departments of
Jon C. D Houtman - Departments of
Peter A Rubenstein - Departments of
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.283(14), pp.9444-9453
DOI: 10.1074/jbc.M709806200
PMID: 18223293
PMCID: PMC2431015
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology
Language: English
Date published: 04/04/2008
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984024421402771

Metrics

15 Record Views

19 Times Cited - Web of Science