Department of Biology James Madison University Harrisonburg Virginia USA
Department of Chemistry and Biochemistry James Madison University Harrisonburg Virginia USA
Department of Biology James Madison University Harrisonburg Virginia USA, Center for Genome and Metagenome Studies James Madison University Harrisonburg Virginia USA
Department of Chemistry and Biochemistry James Madison University Harrisonburg Virginia USA, Center for Genome and Metagenome Studies James Madison University Harrisonburg Virginia USA
The cone‐rod homeobox (CRX) protein is a critical K50 homeodomain transcription factor responsible for the differentiation and maintenance of photoreceptor neurons in the vertebrate retina. Mutant alleles in the human gene encoding CRX result in a variety of distinct blinding retinopathies, including retinitis pigmentosa, cone‐rod dystrophy, and Leber congenital amaurosis. Despite the success of using in vitro biochemistry, animal models, and genomics approaches to study this clinically relevant transcription factor over the past 25 years since its initial characterization, there are no high‐resolution structures in the published literature for the CRX protein. In this study, we use bioinformatic approaches and small‐angle X‐ray scattering (SAXS) structural analysis to further understand the biochemical complexity of the human CRX homeodomain (CRX‐HD). We find that the CRX‐HD is a compact, globular monomer in solution that can specifically bind functional cis‐regulatory elements encoded upstream of retina‐specific genes. This study presents the first structural analysis of CRX, paving the way for a new approach to studying the biochemistry of this protein and its disease‐causing mutant protein variants.
Clanor, Penelope‐Marie B., et al. "Structural and functional analysis of the human cone‐rod homeobox transcription factor." Proteins, vol. 90, no. 8, Mar. 2022. https://doi.org/10.1002/prot.26332
Clanor, Penelope‐Marie B., Buchholz, Christine N., Hayes, Jonathan E., Friedman, Michael A., White, Andrew M., Enke, Ray A., & Berndsen, Christopher E. (2022). Structural and functional analysis of the human cone‐rod homeobox transcription factor. Proteins, 90(8). https://doi.org/10.1002/prot.26332
Clanor, Penelope‐Marie B., Buchholz, Christine N., Hayes, Jonathan E., et al., "Structural and functional analysis of the human cone‐rod homeobox transcription factor," Proteins 90, no. 8 (2022), https://doi.org/10.1002/prot.26332
@article{osti_1856277,
author = {Clanor, Penelope‐Marie B. and Buchholz, Christine N. and Hayes, Jonathan E. and Friedman, Michael A. and White, Andrew M. and Enke, Ray A. and Berndsen, Christopher E.},
title = {Structural and functional analysis of the human cone‐rod homeobox transcription factor},
annote = {Abstract The cone‐rod homeobox (CRX) protein is a critical K50 homeodomain transcription factor responsible for the differentiation and maintenance of photoreceptor neurons in the vertebrate retina. Mutant alleles in the human gene encoding CRX result in a variety of distinct blinding retinopathies, including retinitis pigmentosa, cone‐rod dystrophy, and Leber congenital amaurosis. Despite the success of using in vitro biochemistry, animal models, and genomics approaches to study this clinically relevant transcription factor over the past 25 years since its initial characterization, there are no high‐resolution structures in the published literature for the CRX protein. In this study, we use bioinformatic approaches and small‐angle X‐ray scattering (SAXS) structural analysis to further understand the biochemical complexity of the human CRX homeodomain (CRX‐HD). We find that the CRX‐HD is a compact, globular monomer in solution that can specifically bind functional cis‐regulatory elements encoded upstream of retina‐specific genes. This study presents the first structural analysis of CRX, paving the way for a new approach to studying the biochemistry of this protein and its disease‐causing mutant protein variants.},
doi = {10.1002/prot.26332},
url = {https://www.osti.gov/biblio/1856277},
journal = {Proteins},
issn = {ISSN 0887-3585},
number = {8},
volume = {90},
place = {United States},
publisher = {Wiley Blackwell (John Wiley & Sons)},
year = {2022},
month = {03}}