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Biochemistry Seminar – Walter Chazin :”Functional Dynamics of Modular Multi-Domain Proteins”

April 25, 2018 @ 4:00 pm - 5:00 pm

Dr. Walter Chazin

Department of Biochemistry and Chemistry

Vanderbilt University

Title: “Functional Dynamics of Modular Multi-Domain Proteins”


Fundamental processes driving the operation, propagation, and maintenance of cells are carried out by multi-protein machines.  Machines require moving parts and in the case of protein machinery, the movement of the machine’s parts is enabled by making the constituent proteins modular, linking multiple globular domains together with flexible tethers.  Flexibility between domains in these proteins is critical to the movement between the steps that provide the overall output of the machine.  While clearly important for function, inter-domain flexibility poses a significant challenge for structural analysis because the spatial organization of the domains (i.e. the architecture) is not static but rather time dependent.  Our laboratory applies a combination of NMR and SAXS approaches in solution to define the architectural dynamics of modular multi-domain proteins through their trajectory between functional states.  In this presentation I will describe our progress in investigating human DNA replication machinery, characterizing the ubiquitous eukaryotic ssDNA binding protein, replication protein A (RPA), that coats template DNA as it is unwound and the DNA-dependent RNA polymerase, DNA primase, which synthesizes the first ~10 nucleotides of primer on the template.  Our results show how changes in the architectural dynamics can modulate RPA affinity for ssDNA and provide a model for its function as a scaffold at the core of the DNA replication machinery.  They also reveal the trajectory of changes in the architectural dynamics of DNA primase from pre-initiation through elongation and hand-off to polymerase a, suggesting why synthesis of the initial di-nucleotide is the rate-limiting step in initiation and providing insight into changes in configuration and architectural dynamics as it elongates the primer.

Host: Jae-Hyun Cho

Location: 108 Biochemistry Building (Bldg#1507)


April 25, 2018
4:00 pm - 5:00 pm
Event Category:


Jae-Hyun Cho


108 Biochemistry Building (Bldg.#1507)
300 Olsen Blvd
College Station, TX 77845 United States
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