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Structure and function of SET and MYND domain-containing proteins.

Spellmon N, Holcomb J, Trescott L, Sirinupong N, Yang Z - Int J Mol Sci (2015)

Bottom Line: SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domain-containing proteins (SMYD) have been found to methylate a variety of histone and non-histone targets which contribute to their various roles in cell regulation including chromatin remodeling, transcription, signal transduction, and cell cycle control.During early development, SMYD proteins are believed to act as an epigenetic regulator for myogenesis and cardiomyocyte differentiation as they are abundantly expressed in cardiac and skeletal muscle.This review will examine the biological relevance and gather all of the current structural data of SMYD proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA. nicholas.spellmon@wayne.edu.

ABSTRACT
SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domain-containing proteins (SMYD) have been found to methylate a variety of histone and non-histone targets which contribute to their various roles in cell regulation including chromatin remodeling, transcription, signal transduction, and cell cycle control. During early development, SMYD proteins are believed to act as an epigenetic regulator for myogenesis and cardiomyocyte differentiation as they are abundantly expressed in cardiac and skeletal muscle. SMYD proteins are also of therapeutic interest due to the growing list of carcinomas and cardiovascular diseases linked to SMYD overexpression or dysfunction making them a putative target for drug intervention. This review will examine the biological relevance and gather all of the current structural data of SMYD proteins.

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Related in: MedlinePlus

Structure of MYND domains. (A) Structural superposition of the MYND domains of SMYD and AML1/ETO (PDB code: 2ODD). MYND is represented by ribbon and colored in magenta (SMYD1), cyan (SMYD2), yellow (SMYD3), and blue (AML1/ETO). Proline-rich peptide bound to AML1/ETO is depicted by ribbon; (B) Superposition of the peptide binding pockets. Putative peptide interacting residues are colored according to the scheme in (A). The proline-rich peptide bound to AML1/ETO is depicted by balls-and-sticks; and (C) Surface representation of the MYND domains. Coloring is according to the electrostatic potential: red, white, and blue correspond to negative, neutral, and positive potential, respectively. The vacuum electrostatics/protein contact potential was generated by PyMOL. The proline-rich peptide, represented by balls-and-sticks, is modeled by superposition of the MYND domain of SMYD and AML1/ETO.
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ijms-16-01406-f002: Structure of MYND domains. (A) Structural superposition of the MYND domains of SMYD and AML1/ETO (PDB code: 2ODD). MYND is represented by ribbon and colored in magenta (SMYD1), cyan (SMYD2), yellow (SMYD3), and blue (AML1/ETO). Proline-rich peptide bound to AML1/ETO is depicted by ribbon; (B) Superposition of the peptide binding pockets. Putative peptide interacting residues are colored according to the scheme in (A). The proline-rich peptide bound to AML1/ETO is depicted by balls-and-sticks; and (C) Surface representation of the MYND domains. Coloring is according to the electrostatic potential: red, white, and blue correspond to negative, neutral, and positive potential, respectively. The vacuum electrostatics/protein contact potential was generated by PyMOL. The proline-rich peptide, represented by balls-and-sticks, is modeled by superposition of the MYND domain of SMYD and AML1/ETO.

Mentions: MYND domain is a zinc finger motif identified to bind to proline-rich regions serving as a protein–protein interaction module [9,10,38]. In SMYD proteins, the MYND domain is part of the N-terminal lobe that interacts with the catalytic SET domain, but it does not participate in substrate or cofactor binding (Figure 1B) [7,11,12]. Consistently, deletion of the MYND domain does not affect the methyltransferase activity of SMYD2 in vitro, suggesting that the MYND domain is dispensable in methylation [14]. Despite the high sequence similarity to LIM (Lin11-Isl1-Mec3) domains, the MYND domain exhibits a different type of fold. The secondary structure of the MYND domain adopts a β–β–α topology, which is structurally similar to some PHD (Plant Homeo Domain) and RING motifs (Figure 2A). Although the MYND domains from AML1/ETO and SMYD proteins are only 30% identical in the primary sequence, the backbone and chelating zinc centers of the MYND are well superimposed (Figure 2A). The two structures share two anti-parallel β-strands (β6 and β7) and a small kinked α-helix (αA) that organize around two zinc atoms. Seven cysteine residues and one histidine are centered around the two zinc ions in a C4C2HC arrangement.


Structure and function of SET and MYND domain-containing proteins.

Spellmon N, Holcomb J, Trescott L, Sirinupong N, Yang Z - Int J Mol Sci (2015)

Structure of MYND domains. (A) Structural superposition of the MYND domains of SMYD and AML1/ETO (PDB code: 2ODD). MYND is represented by ribbon and colored in magenta (SMYD1), cyan (SMYD2), yellow (SMYD3), and blue (AML1/ETO). Proline-rich peptide bound to AML1/ETO is depicted by ribbon; (B) Superposition of the peptide binding pockets. Putative peptide interacting residues are colored according to the scheme in (A). The proline-rich peptide bound to AML1/ETO is depicted by balls-and-sticks; and (C) Surface representation of the MYND domains. Coloring is according to the electrostatic potential: red, white, and blue correspond to negative, neutral, and positive potential, respectively. The vacuum electrostatics/protein contact potential was generated by PyMOL. The proline-rich peptide, represented by balls-and-sticks, is modeled by superposition of the MYND domain of SMYD and AML1/ETO.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307310&req=5

ijms-16-01406-f002: Structure of MYND domains. (A) Structural superposition of the MYND domains of SMYD and AML1/ETO (PDB code: 2ODD). MYND is represented by ribbon and colored in magenta (SMYD1), cyan (SMYD2), yellow (SMYD3), and blue (AML1/ETO). Proline-rich peptide bound to AML1/ETO is depicted by ribbon; (B) Superposition of the peptide binding pockets. Putative peptide interacting residues are colored according to the scheme in (A). The proline-rich peptide bound to AML1/ETO is depicted by balls-and-sticks; and (C) Surface representation of the MYND domains. Coloring is according to the electrostatic potential: red, white, and blue correspond to negative, neutral, and positive potential, respectively. The vacuum electrostatics/protein contact potential was generated by PyMOL. The proline-rich peptide, represented by balls-and-sticks, is modeled by superposition of the MYND domain of SMYD and AML1/ETO.
Mentions: MYND domain is a zinc finger motif identified to bind to proline-rich regions serving as a protein–protein interaction module [9,10,38]. In SMYD proteins, the MYND domain is part of the N-terminal lobe that interacts with the catalytic SET domain, but it does not participate in substrate or cofactor binding (Figure 1B) [7,11,12]. Consistently, deletion of the MYND domain does not affect the methyltransferase activity of SMYD2 in vitro, suggesting that the MYND domain is dispensable in methylation [14]. Despite the high sequence similarity to LIM (Lin11-Isl1-Mec3) domains, the MYND domain exhibits a different type of fold. The secondary structure of the MYND domain adopts a β–β–α topology, which is structurally similar to some PHD (Plant Homeo Domain) and RING motifs (Figure 2A). Although the MYND domains from AML1/ETO and SMYD proteins are only 30% identical in the primary sequence, the backbone and chelating zinc centers of the MYND are well superimposed (Figure 2A). The two structures share two anti-parallel β-strands (β6 and β7) and a small kinked α-helix (αA) that organize around two zinc atoms. Seven cysteine residues and one histidine are centered around the two zinc ions in a C4C2HC arrangement.

Bottom Line: SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domain-containing proteins (SMYD) have been found to methylate a variety of histone and non-histone targets which contribute to their various roles in cell regulation including chromatin remodeling, transcription, signal transduction, and cell cycle control.During early development, SMYD proteins are believed to act as an epigenetic regulator for myogenesis and cardiomyocyte differentiation as they are abundantly expressed in cardiac and skeletal muscle.This review will examine the biological relevance and gather all of the current structural data of SMYD proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA. nicholas.spellmon@wayne.edu.

ABSTRACT
SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domain-containing proteins (SMYD) have been found to methylate a variety of histone and non-histone targets which contribute to their various roles in cell regulation including chromatin remodeling, transcription, signal transduction, and cell cycle control. During early development, SMYD proteins are believed to act as an epigenetic regulator for myogenesis and cardiomyocyte differentiation as they are abundantly expressed in cardiac and skeletal muscle. SMYD proteins are also of therapeutic interest due to the growing list of carcinomas and cardiovascular diseases linked to SMYD overexpression or dysfunction making them a putative target for drug intervention. This review will examine the biological relevance and gather all of the current structural data of SMYD proteins.

Show MeSH
Related in: MedlinePlus