Structural and functional studies into the ATPase family AAA+ domain-containing protein 2

Presenter's Name(s)

Isabelle Kressy

Abstract

Chromatin consists of DNA densely packed around a nucleosome, which is comprised of an octamer of histones. On each of these histone proteins the N-terminal flexible tails are exposed to chemical modifications. Protein binding to these modifications can alter how tightly DNA is wrapped around the nucleosome, exposing the DNA for transcription and replication processes. Bromodomains are a conserved protein motif that binds to acetylated lysine modifications on histones, which can affect DNA replication and ultimately cell proliferation. The ATPase family AAA+ domain-containing protein 2 (ATAD2) contains a C- terminal bromodomain (BRD) and is known to be up-regulated in many forms of cancer. My goal is to characterize histone binding partners of ATAD2. In this study, we use isothermal titration calorimetry (ITC) to test ligand binding affinities. We hypothesize that the presence of nearby post-translational modifications (PTMs) impacts the ability of the ATAD2 bromodomain to recognize its binding partners. Understanding the role of ATAD2 will lead to further discovery of how it plays a role in processes that lead to cancer and how it can be used as a drug target.

Primary Faculty Mentor Name

Karen Glass

Graduate Student Mentors

Kiera Malone

Status

Undergraduate

Student College

College of Arts and Sciences

Program/Major

Biochemistry

Primary Research Category

Life Sciences

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Structural and functional studies into the ATPase family AAA+ domain-containing protein 2

Chromatin consists of DNA densely packed around a nucleosome, which is comprised of an octamer of histones. On each of these histone proteins the N-terminal flexible tails are exposed to chemical modifications. Protein binding to these modifications can alter how tightly DNA is wrapped around the nucleosome, exposing the DNA for transcription and replication processes. Bromodomains are a conserved protein motif that binds to acetylated lysine modifications on histones, which can affect DNA replication and ultimately cell proliferation. The ATPase family AAA+ domain-containing protein 2 (ATAD2) contains a C- terminal bromodomain (BRD) and is known to be up-regulated in many forms of cancer. My goal is to characterize histone binding partners of ATAD2. In this study, we use isothermal titration calorimetry (ITC) to test ligand binding affinities. We hypothesize that the presence of nearby post-translational modifications (PTMs) impacts the ability of the ATAD2 bromodomain to recognize its binding partners. Understanding the role of ATAD2 will lead to further discovery of how it plays a role in processes that lead to cancer and how it can be used as a drug target.