Biochemistry

Peter Rubenstein, PhD

Portrait

Professor of Biochemistry
Professor of Internal Medicine, Pediatrics

Contact Information

Primary Office: 4-452 BSB
Iowa City, IA 52242
Primary Office Phone: 319-335-7911

Email: peter-rubenstein@uiowa.edu
Web: Rubenstein Laboratory

Education

AB, Biochemistry, University of California, Berkeley
MA, Biochemistry and Molecular Biology, Harvard University
PhD, Biochemistry and Molecular Biology, Harvard University

Post Doctoral, Biochemistry & Biophysics, Univ. of California School of Medicine-SF
Post Doctoral, Biochemistry & Biophysics, Univ of California School of Medicine-SF

Education/Training Program Affiliations

Biosciences Graduate Program
Department of Biochemistry PhD
Interdisciplinary Graduate Program in Molecular and Cellular Biology
Interdisciplinary Graduate Program in Translational Biomedicine
Medical Scientist Training Program

Research Summary

Our laboratory investigates the biochemistry of actin and the actin binding proteins that modulate its function within the cell. In particular, we are interested in the conformational changes in actin necessary for its polymerization, the forces that stabilize actin monomers within the actin filament, and the manner in which actin filament modulating proteins such as cofilin, Arp2/3 complex and profilin carry out their roles. Our approach is to use yeast actin and the yeast actin cytoskeleton as a model system. Based on hypotheses concerning actin function and actin dynamics, we make mutant actin constructs using site-directed mutagenesis, express the actin in yeast as the only actin in the cell, and determine phenotypes associated with the actin mutation such as altered growth rate, altered endocytosis, and altered actin deposition. We then purify the actin and determine its in vitro behavior using a series of biochemical and biophysical approaches such as electron microscopy and fluorescence spectroscopy. We then try to correlate the effects of the mutations we observe in vitro with the phenotypes associated with these mutations in vivo. With this basic system, we are currently focusing on two projects. We have shown that although the proteins are 90% identical, muscle and yeast actins display distinct differences in their kinetics and ability to interact with different actin binding proteins that can have a substantial effect on actin filament dynamics. To investigate the basis for these differences, we have made a set of yeast/muscle hybrid actins with one yeast half and one muscle half to try to determine which part of the actin is responsible for the behavioral differences seen between the two parent actins. Second, it has been found that six different actin mutations cause autosomal dominant hearing loss in humans. We have cloned each of these into yeast actin and are assessing the effects of these mutations in vivo and in vitro with the goal of gaining insight into altered actin interactions that might result in deafness.

Selected Publications

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Bergeron S, Wedemeyer E, Lee R, Wen K, McKane M, Pierick A, Berger A, Rubenstein P, Bartlett H.  Allele-specific effects of thoracic aortic aneurysm and dissection alpha-smooth muscle actin mutations on actin function.  The Journal of Biological Chemistry.  2011 April. 286(13):11356-69.
[PubMed]

Wen K, McKane M, Stokasimov E, Fields J, Rubenstein P.  A potential yeast actin allosteric conduit dependent on hydrophobic core residues val-76 and trp-79.  The Journal of Biological Chemistry.  2010 July. 285(27):21185-94.
[PubMed]

Bergeron S, Zhu M, Thiem S, Friderici K, Rubenstein P.  Ion-dependent polymerization differences between mammalian beta- and gamma-nonmuscle actin isoforms.  The Journal of Biological Chemistry.  2010 May. 285(21):16087-95.
[PubMed]

Wen K, Rubenstein P, DeMali K.  Vinculin nucleates actin polymerization and modifies actin filament structure.  The Journal of Biological Chemistry.  2009 October. 284(44):30463-73.
[PubMed]

Stokasimov E, Rubenstein P.  Actin isoform-specific conformational differences observed with hydrogen/deuterium exchange and mass spectrometry.  The Journal of Biological Chemistry.  2009 September. 284(37):25421-30.
[PubMed]

Morín M, Bryan K, Mayo-Merino F, Goodyear R, Mencía A, Modamio-Høybjør S, del Castillo I, Cabalka J, Richardson G, Moreno F, Rubenstein P.  In vivo and in vitro effects of two novel gamma-actin (ACTG1) mutations that cause DFNA20/26 hearing impairment.  Human Molecular Genetics.  2009 August. 18(16):3075-89.
[PubMed]

Bryan K, Rubenstein P.  Allele-specific effects of human deafness gamma-actin mutations (DFNA20/26) on the actin/cofilin interaction.  The Journal of Biological Chemistry.  2009 July. 284(27):18260-9.
[PubMed]

Wen K, Rubenstein P.  Differential regulation of actin polymerization and structure by yeast formin isoforms.  The Journal of Biological Chemistry.  2009 June. 284(25):16776-83.
[PubMed]

Scoville D, Stamm J, Altenbach C, Shvetsov A, Kokabi K, Rubenstein P, Hubbell W, Reisler E.  Effects of binding factors on structural elements in F-actin.  Biochemistry.  2009 January. 48(2):370-8.
[PubMed]

Stokasimov E, McKane M, Rubenstein P.  Role of intermonomer ionic bridges in the stabilization of the actin filament.  The Journal of Biological Chemistry.  2008 December. 283(50):34844-54.
[PubMed]

Date Last Modified: 06/07/2014 - 21:56:23