7z5k

Transcription factor MYF5 bound to non-symmetrical siteTranscription factor MYF5 bound to non-symmetrical site

Structural highlights

7z5k is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.28Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MYF5_HUMAN The disease is caused by variants affecting the gene represented in this entry.

Function

MYF5_HUMAN Transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation (PubMed:29887215). Together with MYOG and MYOD1, co-occupies muscle-specific gene promoter core region during myogenesis. Induces fibroblasts to differentiate into myoblasts. Probable sequence specific DNA-binding protein.^[1] ^[2]

Publication Abstract from PubMed

Transcription factors (TFs) recognize specific bases within their DNA-binding motifs, with each base contributing nearly independently to total binding energy. However, the energetic contributions of particular dinucleotides can deviate strongly from the additive approximation, indicating that some TFs can specifically recognize DNA dinucleotides. Here we solved high-resolution (<1 A) structures of MYF5 and BARHL2 bound to DNAs containing sets of dinucleotides that have different affinities to the proteins. The dinucleotides were recognized either enthalpically, by an extensive water network that connects the adjacent bases to the TF, or entropically, by a hydrophobic patch that maintained interfacial water mobility. This mechanism confers differential temperature sensitivity to the optimal sites, with implications for thermal regulation of gene expression. Our results uncover the enigma of how TFs can recognize more complex local features than mononucleotides and demonstrate that water-mediated recognition is important for predicting affinities of macromolecules from their sequence.

Interfacial water confers transcription factors with dinucleotide specificity.,Morgunova E, Nagy G, Yin Y, Zhu F, Nayak SP, Xiao T, Sokolov I, Popov A, Laughton C, Grubmuller H, Taipale J Nat Struct Mol Biol. 2025 Jan 3. doi: 10.1038/s41594-024-01449-6. PMID:39753777^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Braun T, Buschhausen-Denker G, Bober E, Tannich E, Arnold HH. A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts. EMBO J. 1989 Mar;8(3):701-9. PMID:2721498 doi:10.1002/j.1460-2075.1989.tb03429.x
↑ Di Gioia SA, Shaaban S, Tüysüz B, Elcioglu NH, Chan WM, Robson CD, Ecklund K, Gilette NM, Hamzaoglu A, Tayfun GA, Traboulsi EI, Engle EC. Recessive MYF5 Mutations Cause External Ophthalmoplegia, Rib, and Vertebral Anomalies. Am J Hum Genet. 2018 Jul 5;103(1):115-124. PMID:29887215 doi:10.1016/j.ajhg.2018.05.003
↑ Morgunova E, Nagy G, Yin Y, Zhu F, Nayak SP, Xiao T, Sokolov I, Popov A, Laughton C, Grubmuller H, Taipale J. Interfacial water confers transcription factors with dinucleotide specificity. Nat Struct Mol Biol. 2025 Jan 3. PMID:39753777 doi:10.1038/s41594-024-01449-6

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OCA

[1] Braun T, Buschhausen-Denker G, Bober E, Tannich E, Arnold HH. A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts. EMBO J. 1989 Mar;8(3):701-9. PMID:2721498 doi:10.1002/j.1460-2075.1989.tb03429.x

[2] Di Gioia SA, Shaaban S, Tüysüz B, Elcioglu NH, Chan WM, Robson CD, Ecklund K, Gilette NM, Hamzaoglu A, Tayfun GA, Traboulsi EI, Engle EC. Recessive MYF5 Mutations Cause External Ophthalmoplegia, Rib, and Vertebral Anomalies. Am J Hum Genet. 2018 Jul 5;103(1):115-124. PMID:29887215 doi:10.1016/j.ajhg.2018.05.003

[3] Morgunova E, Nagy G, Yin Y, Zhu F, Nayak SP, Xiao T, Sokolov I, Popov A, Laughton C, Grubmuller H, Taipale J. Interfacial water confers transcription factors with dinucleotide specificity. Nat Struct Mol Biol. 2025 Jan 3. PMID:39753777 doi:10.1038/s41594-024-01449-6

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