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Understanding the structural basis of RFX complex in regulating MHC gene expression


EMSL Project ID
51295

Abstract

The Major Histocompatibility complex (MHC) is critical in immune system for T cell maturation and self vs nonself discrimination, thus expression of MHC genes has to be tightly regulated. Active transcription of MHC is initiated by multiple transcription factors, including RFX complex, CREB, NF-Y complex, CIITA and NLRC5. RFX complex specifically recognizes the conserved X-motif DNA, which is essential for the recruitment of all other transcription factors to the promoter region. Even though it was identified early at 1990s, the architecture of RFX complex and DNA recognition mechanism are still unknown. Here we propose to use cryo-EM to study RFX complex, which will provide fundamental knowledge in understanding the RFX superfamily, illustrate the mechanism of MHC gene transcription and provide structural guidance for drug development to treat the immunodeficiency disease caused by RFX mutation.

Project Details

Start Date
2020-03-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Liman Zhang
Institution
Oregon Health & Science University

Team Members

Sean Mulligan
Institution
Oregon Health & Science University

Bhaskar Paidimuddala
Institution
Oregon Health & Science University

Jianhao Cao
Institution
Oregon Health & Science University

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory

Trevor Moser
Institution
Environmental Molecular Sciences Laboratory