Biophysical Studies and NMR Structure of the Interaction between RFX5 and RFXAP: Insights into the Transcription Complex that Regulates the Mammalian Immune Response

Title	Biophysical Studies and NMR Structure of the Interaction between RFX5 and RFXAP: Insights into the Transcription Complex that Regulates the Mammalian Immune Response
Author	Laird, Kholiswa M.
Advisors	Garvie, Colin W; Summers, Michael F
Program	Chemistry
UMBC Department	Chemical and Biochemical Engineering
Document Type	dissertation
Sponsors	University of Maryland, Baltimore County (UMBC)
Keywords	MHCII; NMR; Protein; RFX; Transcription
Date Issued	2009-01-01
Abstract	The human adaptive immune response is regulated by major histocompatibility complex class II (MHCII) molecules. Initiation of the immune response against infection is directly related to the level of expression of MHCII molecules in the cell. A multi-protein complex, termed the MHCII enhanceosome, is responsible for the expression of MHCII genes. The key DNA binding component of the MHCII enhanceosome is the RFX complex. The RFX complex is comprised of three proteins - RFX5, RFXAP, and RFXB - all of which are required for DNA binding and assembly of the enhanceosome. Mutations or deletions in any of the RFX proteins that prevent RFX assembly or the recruitment of other proteins in the MHCII enhanceosome, results in a severe immunodeficiency disorder. RFX5 is comprised of four domains: the oligomerization domain, the RFX DNA binding domain, the dimerization domain, and the transactivation domain. RFX5 dimerizes through both the oligomerization domain and the dimerization domain, and this dimerization has been shown to be essential for RFX complex assembly. The oligomerization domain of RFX5 is also sufficient to interact with RFXAP. This thesis describes crystallographic studies performed on the dimerization domain of RFX5 to determine how it induces dimerization of RFX5. It also describes mutational studies of the oligomerization domain of RFX5 that influences the oligomeric state of RFX5 and its interaction with RFXAP. Finally, we describe the solution structure of the oligomerization domain of RFX5 bound to the interaction domain of RFXAP. These studies answer a number of questions posed by previous in vivo and in vitro studies and give a valuable insight into how the RFX complex assembles.
Identifier	10201
Format	application:pdf
Language	en
Collection	UMBC Theses and Disserations.
Rights Statement	This item may be protected under Title 17 of the U.S. Copyright Law. It is made available by UMBC for non-commercial research and education. For permission to publish or reproduce, please see http://aok.lib.umbc.edu/specoll/repro.php or contact Special Collections at speccoll(at)umbc.edu.
Source	Laird_umbc_0434D_10201.pdf

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Biophysical Studies and NMR Structure of the Interaction between RFX5 and RFXAP: Insights into the Transcription Complex that Regulates the Mammalian Immune Response

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