The SRF/NKX 2.5 Regulatory Node

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2019

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Abstract

Serum Response Factor, SRF, is a regulatory protein that helps with the process of gene transcription. SRF binds to DNA sequences called Serum Response Elements (SRE). A model of SRF and NKX 2.5 was constructed to understand the feasibility and scope of my proposed project. The x-ray crystal structures of the proteins used for SRF and NKX 2.5 were 1HBX and 3RKQ, respectively. SRF was bound on the opposite side of the DNA relative to NKX 2.5 based on our sequence alignment. This configuration makes the preliminary model plausible. The two proteins was loaded into the program Pymol: “fetch 1hbx” and “fetch 3rkq” chain W from 1HBX will be aligned with chain C from 3RKQ and their residues will be from -4 to -3 and 2 to 8, respectively. Then aligned based on the selected residues for each chain, so the subsequent command will be: “align 1hbx_resid_-4-3, 3rkq_resid_2-8.” The model showed NKX 2.5 and SRF were trans to each other meaning SRF was on the opposite side of DNA from NKX 2.5. It was seen that two strands from NKX 2.5 and SRF went down the same groove leading to a steric clash or potentially leading to conformational change. Transcription regulation by direct and mutated TF could spawn a new class of therapeutic agents. The action of SRF can be nudged toward proliferation or conversely nudged toward differentiation. Both effects could have a significant impact on wound healing and heart repair.

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