Tag Archive for Oliver

Mukerji, Oliver Co-Author Study in PNAS on Basic Cell Function

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In this illustration, SecA is shown in light gray and the SecYEG complex is in dark gray. The rainbow colored portion of SecA is the two helix finger. n cyan is a model of the hairpin.

In this illustration, the hairpin is highlighted in cyan. The hairpin is formed by the initiator part of a protein.

All cells — bacterial or human — secrete up to 10 or 20 percent of the proteins that they make. Human secreted proteins, for example, include components of serum, hormones, growth factors that promote cell development during embryogenesis and tissue remodeling, and proteins that provide the basis for immune cell signaling during infection or when fighting cancer.

The secretion process, however, isn’t an easy feat for cells, as they need to move the proteins across a membrane through a channel. Transport requires the formation of a hairpin, formed by an initiator protein.

In a recent study, Don Oliver, the Daniel Ayres Professor of Biology, professor of molecular biology and biochemistry, and Ishita Mukerji, the Fisk Professor of Natural Science, professor of molecular biology and biochemistry, explain the importance of where and why hairpins form and how they help proteins move across the cell.

The study, titled “Alignment of the protein substrate hairpin along the SecA two-helix finger primes protein transport in Escherichia coli,” brings together key areas of membrane biochemistry, structural biology and molecular biophysics, and has innovative applications of molecular genetics and fluorescence spectroscopy. It was published in the Aug. 7 issue of Proceedings of the National Academy of Sciences (PNAS).

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Oliver Honored with NIH Award for Protein Translocation Research

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Don Oliver

Don Oliver

Professor Don Oliver received a three-year grant from the National Institutes of Health (NIH) Academic Research Enhancement Award (AREA) (R15) for his research titled “Mechanism of SecA-dependent protein translocation.” The grant, worth $374,148, was awarded on April 15.

Oliver is the Daniel Ayres Professor of Biology and professor of molecular biology and biochemistry.

Oliver studies how proteins are targeted to and transported across biological membranes utilizing bacteria as a simple model system.”The current genetic and biochemical studies are designed to elucidate a molecular motor protein, SecA ATPase, that drives proteins through a universally conserved protein-conducting channel by a largely unknown molecular mechanism,” he said.  “Clarification of the transport mechanism by this motor and its interplay with the channel is essential for understanding comparable protein transport systems in higher cells.”

In addition, such studies should allow for the development of novel antibacterial agents against SecA in order to combat the spread of multi-drug resistant bacterial pathogens.

The grant funds will be utilized to support two Ph.D. Students, a BA/MA fifth-year student, and four undergraduate research students that comprise of Oliver’s research group.

Hingorani Group Publishes 8 Papers on DNA Mismatch Repair

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A research group led by Manju Hingorani, associate professor of molecular biology and biochemistry, has published eight papers in 2011-2012 on the mechanisms of DNA replication and repair proteins, independently and in collaboration with research groups at Wesleyan and other national and international universities.

The papers are:

“Large conformational changes in MutS during DNA scanning, mismatch recognition and repair signaling,” published in The EMBO Journal, 2012 (in press).

“The Variable Sub-domain of Escherichia coli SecA functions to regulate in the SecA ATPase Activity and ADP release,” published in the Journal of Bacteriology, 2012 (March 2 Epub). Don Oliver, the Daniel Ayres Professor of Biology, professor of molecular biology and biochemistry, was the lead investigator and Fred Cohan, professor of biology, professor of environmental studies, was a co-author on this paper.

“Single-molecule multiparameter fluorescence spectroscopy reveals directional MutS binding to mismatched bases in DNA,” published in Nucleic Acids Research, 2012 (Feb, 24 Epub).

“Biochemical analysis of the human mismatch repair proteins hMutSαMSH2G674A-MSH6 and MSH2-MSH6T1219D,” published in the Journal of Biological Chemistry, 2012 (Jan. 25 Epub).

“ATP Binding and Hydrolysis-Driven Rate-Determining Events in the RFC-Catalyzed PCNA Clamp Loading Reaction,” published in the Journal of Molecular Biology, Feb. 17, 2012; 416(2), pages 176-91.

“A Central Swivel Point in the RFC Clamp Loader Controls PCNA Opening and Loading on DNA,” published in the Journal of Molecular Biology, Feb. 17, 2012; 416(2), pages 163-75.

“Human MSH2 (hMSH2) protein controls ATP processing by hMSH2-hMSH6,” published in the Journal of Biological Chemistry, Nov. 18, 2011; 286(46), pages 40287-95.

“Dynamical allosterism in the mechanism of action of DNA mismatch repair protein MutS,” published in the Biophysical Journal, Oct. 5, 2011;101(7), pages 1730-9. David Beveridge, the Joshua Boger Professor of the Sciences and Mathematics, was the lead investigator on this paper.