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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

TPR-like C-terminal domain (CTD). (A) Structural superposition of the CTD domains of SMYD and TPR domain of Hop1 (PDB code: 1ELR). SMYD proteins are represented by ribbons and colored according to the scheme in Figure 1C. The Hop1 TPR domain is shown in blue. Hsp90 peptide bound to Hop1 is depicted by balls-and-sticks; (B) Crystal lattice of SMYD1 shows the involvement of the protruding C-terminal α-helix in the crystal packing; and (C) Structural superposition of the CTD domain of SMYD1 and TPR domain of FKBP52 (PDB code: 1QZ2). SMYD1 is colored in purple and FKBP52 in white.
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ijms-16-01406-f006: TPR-like C-terminal domain (CTD). (A) Structural superposition of the CTD domains of SMYD and TPR domain of Hop1 (PDB code: 1ELR). SMYD proteins are represented by ribbons and colored according to the scheme in Figure 1C. The Hop1 TPR domain is shown in blue. Hsp90 peptide bound to Hop1 is depicted by balls-and-sticks; (B) Crystal lattice of SMYD1 shows the involvement of the protruding C-terminal α-helix in the crystal packing; and (C) Structural superposition of the CTD domain of SMYD1 and TPR domain of FKBP52 (PDB code: 1QZ2). SMYD1 is colored in purple and FKBP52 in white.

Mentions: The CTD domain of SMYD proteins contains a series of antiparallel α-helices that display a similar structure to TPR domains despite the lack of sequence identity (Figure 1B). TPR domains are important for binding of cochaperones to Hsp90. For example, the Hop1 TPR domain binds to the very C-terminal end of Hsp90 mediating Hsp90 chaperone activity (Figure 6A) [48,49]. The CTD structure is also well conserved in the SMYD family, and the only chief difference is the extended and protruded αN helix that resembles the “handle” of the wrench-shaped SMYD1 (Figure 6A). This feature is unique to SMYD1, as SMYD2–3 with the shorter αN helix resemble the shape of a clam-like shell. The unique portion of the αN helix in SMYD1 is well conserved from fish to human (data not shown). This region contains a patch of hydrophobic residues that mediate the crystal packing in SMYD1 crystals (Figure 6B). Interestingly, the CTD structure of SMYD1 is similar to the TPR structure of FKBP52 (Figure 6C). In FKBP52, the TPR domain also has a protruding C-terminal helix that contains a putative binding site for calmodulin [50,51]. The function of the unique SMYD1 C-terminal helical tail is unknown, but the conserved sequence and involvement in the crystal packing suggests that it may serve as a site for protein–protein interaction.


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)

TPR-like C-terminal domain (CTD). (A) Structural superposition of the CTD domains of SMYD and TPR domain of Hop1 (PDB code: 1ELR). SMYD proteins are represented by ribbons and colored according to the scheme in Figure 1C. The Hop1 TPR domain is shown in blue. Hsp90 peptide bound to Hop1 is depicted by balls-and-sticks; (B) Crystal lattice of SMYD1 shows the involvement of the protruding C-terminal α-helix in the crystal packing; and (C) Structural superposition of the CTD domain of SMYD1 and TPR domain of FKBP52 (PDB code: 1QZ2). SMYD1 is colored in purple and FKBP52 in white.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-16-01406-f006: TPR-like C-terminal domain (CTD). (A) Structural superposition of the CTD domains of SMYD and TPR domain of Hop1 (PDB code: 1ELR). SMYD proteins are represented by ribbons and colored according to the scheme in Figure 1C. The Hop1 TPR domain is shown in blue. Hsp90 peptide bound to Hop1 is depicted by balls-and-sticks; (B) Crystal lattice of SMYD1 shows the involvement of the protruding C-terminal α-helix in the crystal packing; and (C) Structural superposition of the CTD domain of SMYD1 and TPR domain of FKBP52 (PDB code: 1QZ2). SMYD1 is colored in purple and FKBP52 in white.
Mentions: The CTD domain of SMYD proteins contains a series of antiparallel α-helices that display a similar structure to TPR domains despite the lack of sequence identity (Figure 1B). TPR domains are important for binding of cochaperones to Hsp90. For example, the Hop1 TPR domain binds to the very C-terminal end of Hsp90 mediating Hsp90 chaperone activity (Figure 6A) [48,49]. The CTD structure is also well conserved in the SMYD family, and the only chief difference is the extended and protruded αN helix that resembles the “handle” of the wrench-shaped SMYD1 (Figure 6A). This feature is unique to SMYD1, as SMYD2–3 with the shorter αN helix resemble the shape of a clam-like shell. The unique portion of the αN helix in SMYD1 is well conserved from fish to human (data not shown). This region contains a patch of hydrophobic residues that mediate the crystal packing in SMYD1 crystals (Figure 6B). Interestingly, the CTD structure of SMYD1 is similar to the TPR structure of FKBP52 (Figure 6C). In FKBP52, the TPR domain also has a protruding C-terminal helix that contains a putative binding site for calmodulin [50,51]. The function of the unique SMYD1 C-terminal helical tail is unknown, but the conserved sequence and involvement in the crystal packing suggests that it may serve as a site for protein–protein interaction.

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