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Solution structure and Rpn1 interaction of the UBL domain of human RNA polymerase II C-terminal domain phosphatase.

Yun JH, Ko S, Lee CK, Cheong HK, Cheong C, Yoon JB, Lee W - PLoS ONE (2013)

Bottom Line: The UBL domain of hUBLCP1 has a unique β-strand (β3) and β3-α2 loop, instead of the canonical β4 observed in other UBL domains.The molecular topology and secondary structures are different from those of known UBL domains including that of fly UBLCP1.The positively charged residues of the β3-α2 loop are involved in interacting with the C-terminal leucine-rich repeat-like domain of Rpn1.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.

ABSTRACT
The ubiquitin-like modifier (UBL) domain of ubiquitin-like domain proteins (UDPs) interacts specifically with subunits of the 26 S proteasome. A novel UDP, ubiquitin-like domain-containing C-terminal domain phosphatase (UBLCP1), has been identified as an interacting partner of the 26 S proteasome. We determined the high-resolution solution structure of the UBL domain of human UBLCP1 by nuclear magnetic resonance spectroscopy. The UBL domain of hUBLCP1 has a unique β-strand (β3) and β3-α2 loop, instead of the canonical β4 observed in other UBL domains. The molecular topology and secondary structures are different from those of known UBL domains including that of fly UBLCP1. Data from backbone dynamics shows that the β3-α2 loop is relatively rigid although it might have intrinsic dynamic profile. The positively charged residues of the β3-α2 loop are involved in interacting with the C-terminal leucine-rich repeat-like domain of Rpn1.

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Structural comparison of the UBL domains.(A) Sequence alignment and secondary structures of the UBL domain of hUBLCP1, ubiquitin, hHR23a, hPLIC-2, and parkin. (B) Structural overlay of the β3-α2 loop of the UBL domain (red) of hUBLCP1 with that of ubiquitin (blue-white), hHR23a (pale cyan), hPLIC-2 (light blue), and Parkin (white-gray), respectively. (C) Sequence alignment and secondary structures of the UBL domains of human (hUBLCP1) and D. melanogaster (DmUBLCP1) UBLCP1. (D) Structural comparison of the UBL domains of human and D. melanogaster UBLCP1. (E) Superposition of the β3-α2 loop regions of the UBL domains of hUBLCP1 (red) and dmUBLCP1 (pale cyan).
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pone-0062981-g002: Structural comparison of the UBL domains.(A) Sequence alignment and secondary structures of the UBL domain of hUBLCP1, ubiquitin, hHR23a, hPLIC-2, and parkin. (B) Structural overlay of the β3-α2 loop of the UBL domain (red) of hUBLCP1 with that of ubiquitin (blue-white), hHR23a (pale cyan), hPLIC-2 (light blue), and Parkin (white-gray), respectively. (C) Sequence alignment and secondary structures of the UBL domains of human (hUBLCP1) and D. melanogaster (DmUBLCP1) UBLCP1. (D) Structural comparison of the UBL domains of human and D. melanogaster UBLCP1. (E) Superposition of the β3-α2 loop regions of the UBL domains of hUBLCP1 (red) and dmUBLCP1 (pale cyan).

Mentions: The molecular topology of the UBL domain of hUBLCP1 was quite different from that of the canonical UBL domain (Fig. 1B), especially in the organization of the secondary structures (β3 and β4; Fig. 2A and Fig. 2B). The pairwise RMSDs of Cα of ubiquitin and the UBL domains of hHR23a, hPLIC-2, and parkin with respect to that of hUBLCP1 were 2.405 Å, 1.391 Å, 3.457 Å, and 3.785 Å, respectively. The fourth strand (β4) in the other UBLs was not observed in hUBLCP1; however, a unique β3-α2 loop was observed in that region (Fig. 1B and Fig. 2A). In addition, unlike other UBL domains, the UBL domain of hUBLCP1 has a short β3, comprising residues Q43, K44, and L45. Most of the unique β3-α2 loop in UBLCP11–81 is exposed to the solvent (Fig. 2B). Very recently, the crystal structure of dmUBLCP1 derived from Drosophila melanogaster was reported [10]. Although the UBL domain of dmUBLCP1 has a high percentage of sequence identity (54%) with that of human UBLCP1, dramatic differences between the two structures were observed (Fig. 2C, 2D, and 2E). Surprisingly, two α-helices (α1 and α2) are connected by a short linker in the UBL domain of the dmUBLCP1. This is very unusual because α2 is located far from α1 (next to β3/β4) in most of the UBL domains, including that of hUBLCP1 (Fig. 2A, 2B, and Fig. S1). However, the structural folds in the UBL domains of hUBLCP1 and dmUBLCP1 are very similar, consistent with the backbone RMSD between the two structures of 1.778 Å (Fig. 2D).


Solution structure and Rpn1 interaction of the UBL domain of human RNA polymerase II C-terminal domain phosphatase.

Yun JH, Ko S, Lee CK, Cheong HK, Cheong C, Yoon JB, Lee W - PLoS ONE (2013)

Structural comparison of the UBL domains.(A) Sequence alignment and secondary structures of the UBL domain of hUBLCP1, ubiquitin, hHR23a, hPLIC-2, and parkin. (B) Structural overlay of the β3-α2 loop of the UBL domain (red) of hUBLCP1 with that of ubiquitin (blue-white), hHR23a (pale cyan), hPLIC-2 (light blue), and Parkin (white-gray), respectively. (C) Sequence alignment and secondary structures of the UBL domains of human (hUBLCP1) and D. melanogaster (DmUBLCP1) UBLCP1. (D) Structural comparison of the UBL domains of human and D. melanogaster UBLCP1. (E) Superposition of the β3-α2 loop regions of the UBL domains of hUBLCP1 (red) and dmUBLCP1 (pale cyan).
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Related In: Results  -  Collection

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pone-0062981-g002: Structural comparison of the UBL domains.(A) Sequence alignment and secondary structures of the UBL domain of hUBLCP1, ubiquitin, hHR23a, hPLIC-2, and parkin. (B) Structural overlay of the β3-α2 loop of the UBL domain (red) of hUBLCP1 with that of ubiquitin (blue-white), hHR23a (pale cyan), hPLIC-2 (light blue), and Parkin (white-gray), respectively. (C) Sequence alignment and secondary structures of the UBL domains of human (hUBLCP1) and D. melanogaster (DmUBLCP1) UBLCP1. (D) Structural comparison of the UBL domains of human and D. melanogaster UBLCP1. (E) Superposition of the β3-α2 loop regions of the UBL domains of hUBLCP1 (red) and dmUBLCP1 (pale cyan).
Mentions: The molecular topology of the UBL domain of hUBLCP1 was quite different from that of the canonical UBL domain (Fig. 1B), especially in the organization of the secondary structures (β3 and β4; Fig. 2A and Fig. 2B). The pairwise RMSDs of Cα of ubiquitin and the UBL domains of hHR23a, hPLIC-2, and parkin with respect to that of hUBLCP1 were 2.405 Å, 1.391 Å, 3.457 Å, and 3.785 Å, respectively. The fourth strand (β4) in the other UBLs was not observed in hUBLCP1; however, a unique β3-α2 loop was observed in that region (Fig. 1B and Fig. 2A). In addition, unlike other UBL domains, the UBL domain of hUBLCP1 has a short β3, comprising residues Q43, K44, and L45. Most of the unique β3-α2 loop in UBLCP11–81 is exposed to the solvent (Fig. 2B). Very recently, the crystal structure of dmUBLCP1 derived from Drosophila melanogaster was reported [10]. Although the UBL domain of dmUBLCP1 has a high percentage of sequence identity (54%) with that of human UBLCP1, dramatic differences between the two structures were observed (Fig. 2C, 2D, and 2E). Surprisingly, two α-helices (α1 and α2) are connected by a short linker in the UBL domain of the dmUBLCP1. This is very unusual because α2 is located far from α1 (next to β3/β4) in most of the UBL domains, including that of hUBLCP1 (Fig. 2A, 2B, and Fig. S1). However, the structural folds in the UBL domains of hUBLCP1 and dmUBLCP1 are very similar, consistent with the backbone RMSD between the two structures of 1.778 Å (Fig. 2D).

Bottom Line: The UBL domain of hUBLCP1 has a unique β-strand (β3) and β3-α2 loop, instead of the canonical β4 observed in other UBL domains.The molecular topology and secondary structures are different from those of known UBL domains including that of fly UBLCP1.The positively charged residues of the β3-α2 loop are involved in interacting with the C-terminal leucine-rich repeat-like domain of Rpn1.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.

ABSTRACT
The ubiquitin-like modifier (UBL) domain of ubiquitin-like domain proteins (UDPs) interacts specifically with subunits of the 26 S proteasome. A novel UDP, ubiquitin-like domain-containing C-terminal domain phosphatase (UBLCP1), has been identified as an interacting partner of the 26 S proteasome. We determined the high-resolution solution structure of the UBL domain of human UBLCP1 by nuclear magnetic resonance spectroscopy. The UBL domain of hUBLCP1 has a unique β-strand (β3) and β3-α2 loop, instead of the canonical β4 observed in other UBL domains. The molecular topology and secondary structures are different from those of known UBL domains including that of fly UBLCP1. Data from backbone dynamics shows that the β3-α2 loop is relatively rigid although it might have intrinsic dynamic profile. The positively charged residues of the β3-α2 loop are involved in interacting with the C-terminal leucine-rich repeat-like domain of Rpn1.

Show MeSH
Related in: MedlinePlus