IBS: an illustrator for the presentation and visualization of biological sequences

Liu, Wenzhong; Xie, Yubin; Ma, Jiyong; Luo, Xiaotong; Nie, Peng; Zuo, Zhixiang; Lahrmann, Urs; Zhao, Qi; Zheng, Yueyuan; Zhao, Yong; Xue, Yu; Ren, Jian

doi:10.1093/bioinformatics/btv362

Cited by 834 publications

(591 citation statements)

References 4 publications

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“…S1) of the individually purified CCHC zinc finger with that of the longer, freshly prepared construct, we observed that the two spectra overlay well, indicating that the CCHC zinc finger is an independent folded domain that does not interact FIGURE 1. (A) Domain organization of S. cerevisiae Pcf11, drawn with IBS (Liu et al 2015). (B) Sequence alignment versus secondary structure for the C terminus of Pcf11 from S. cerevisiae to H. sapiens, drawn with ESPript (Robert and Gouet 2014).…”

Section: Resultsmentioning

confidence: 99%

The C terminus of Pcf11 forms a novel zinc-finger structure that plays an essential role in mRNA 3′-end processing

Yang

Hsu

Lee

et al. 2016

RNA

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3′ -End processing of pre-mRNAs prior to packaging and export to the cytoplasm of the mature transcript is a highly regulated process executed by several tens of protein factors that recognize poorly conserved RNA signals. Among them is Pcf11, a highly conserved, multidomain protein that links transcriptional elongation, 3′ -end processing, and transcription termination. Here we report the structure and biochemical function of Pcf11's C-terminal domain, which is conserved from yeast to humans. We identify a novel zinc-finger fold, resembling a trillium flower. Structural, biochemical, and genetic analyses reveal a highly conserved surface that plays a critical role in both cleavage and polyadenylation. These findings provide further insight into this important protein and its multiple functional roles during cotranscriptional RNA processing.

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Section: Resultsmentioning

confidence: 99%

The C terminus of Pcf11 forms a novel zinc-finger structure that plays an essential role in mRNA 3′-end processing

Yang

Hsu

Lee

et al. 2016

RNA

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“…Structure and sequence analysis of SART3. A, domain architecture of USP15 and SART3, prepared using IBS software (38). The flat-ended blue, green, and magenta lines indicate the constructs used for crystallization.…”

Section: Sart3 Is a Dimer Containing 12 Hat Repeats-mentioning

confidence: 99%

Structural Basis of the Recruitment of Ubiquitin-specific Protease USP15 by Spliceosome Recycling Factor SART3

Zhang

Harding

Hou

et al. 2016

Journal of Biological Chemistry

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Ubiquitin-specific proteases (USPs) USP15 and USP4 belong to a subset of USPs featuring an N-terminal tandem domain in USP (DUSP) and ubiquitin-like (UBL) domain. Squamous cell carcinoma antigen recognized by T-cell 3 (SART3), a spliceosome recycling factor, binds to the DUSP-UBL domain of USP15 and USP4, recruiting them to the nucleus from the cytosol to control deubiquitination of histone H2B and spliceosomal proteins, respectively. To provide structural insight, we solved crystal structures of SART3 in the apo-form and in complex with the DUSP-UBL domain of USP15 at 2.0 and 3.0 Å, respectively. Structural analysis reveals SART3 contains 12 half-a-tetratricopeptide (HAT) repeats, organized into two subdomains, HAT-N and HAT-C. SART3 dimerizes through the concave surface of HAT-C, whereas the HAT-C convex surface binds USP15 in a novel bipartite mode. Isothermal titration calorimetry measurements and mutagenesis analysis confirmed key residues of USP15 involved in the interaction and indicated USP15 binds 20-fold stronger than USP4.Ubiquitination plays an important role in almost every biological process, including protein homeostasis, DNA damage response, gene transcription, protein trafficking, and RNA splicing. Deubiquitinases (DUBs) 2 remove covalently conjugated ubiquitin tags from substrates and regulate ubiquitin signaling. Ubiquitin-specific proteases (USPs) comprise the largest family of DUBs. In addition to the catalytic domain, most USPs contain auxiliary domains that are involved in substrate recognition, activity regulation, or recruitment of binding partners (1, 2). USP4, USP11, and USP15 are a small set of closely related USPs, sharing a similar domain architecture as follows: a DUSP (domain in USP), followed by a ubiquitin-like (UBL) and a large catalytic domain, bifurcated by a second UBL domain and disordered region (Fig. 1A). Evolutionary analysis suggests the three USPs arose from gene duplication events (3). USP4 and USP15 are more closely related in both sequence and function compared with USP11. Both USP4 and USP15 are implicated in mRNA processing through their interaction with spliceosome components (1). USP4 is recruited by U4/U6 small nuclear RNA recycling factor SART3 (squamous cell carcinoma antigen recognized by T cells 3) to remove the Lys-63-polyubiquitin chain from pre-mRNA processing factor 3 (Prp3), and it controls the assembly of the spliceosome at distinct stages of the splicing process (4). USP15, but not USP4, is recruited by SART3 to regulate deubiquitination of free ubiquitinated histone H2B that has been evicted from the nucleosome during transcription (5).SART3 is the mammalian homolog of yeast Prp24 protein and is essential for the formation of U4/U6 small nuclear ribonucleoprotein complex (6). SART3 plays multiple roles in mRNA splicing, viral and host gene transcription, as well as stem cell survival, proliferation, and differentiation. It is also a potential antigen for cancer immunotherapy (7-9). The biological functions of SART3 have been summarized in a recent c...

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“…Protein hits were assessed individually for the consensus sequence and confirmed in a secondary database search. Illustration of HC1 domains and post-translational modifications was produced using Illustrator for Biological Sciences tool (75). HC1 sequences were aligned using Clustal Omega (76).…”

Section: Methodsmentioning

confidence: 99%

Thrombin Cleavage of Inter-α-inhibitor Heavy Chain 1 Regulates Leukocyte Binding to an Inflammatory Hyaluronan Matrix

Petrey

Motte

2016

Journal of Biological Chemistry

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Edited by Amanda FosangDynamic alterations of the extracellular matrix in response to injury directly modulate inflammation and consequently the promotion and resolution of disease. During inflammation, hyaluronan (HA) is increased at sites of inflammation where it may be covalently modified with the heavy chains (HC) of inter-␣-trypsin inhibitor. Deposition of this unique, pathological form of HA (HC-HA) leads to the formation of cable-like structures that promote adhesion of leukocytes. Naive mononuclear leukocytes bind specifically to inflammation-associated HA matrices but do not adhere to HA constitutively expressed under homeostatic conditions. In this study, we have directly investigated a role for the blood-coagulation protease thrombin in regulating the adhesion of monocytic cells to smooth muscle cells producing an inflammatory matrix. Our data demonstrate that the proteolytic activity of thrombin negatively regulates the adhesion of monocytes to an inflammatory HC-HA complex. This effect is independent of protease-activated receptor activation but requires proteolytic activity toward a novel substrate. Components of HC-HA complexes were predicted to contain conserved thrombin-susceptible cleavage sites based on sequence analysis, and heavy chain 1 (HC1) was confirmed to be a substrate of thrombin. Thrombin treatment is sufficient to cleave HC1 associated with either cell-surface HA or serum inter-␣-trypsin inhibitor. Furthermore, thrombin treatment of the inflammatory matrix leads to dissolution of HC-HA cable structures and abolishes leukocyte adhesion. These data establish a novel mechanism whereby thrombin cleavage of HC1 regulates the adhesive properties of an inflammatory HA matrix.

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IBS: an illustrator for the presentation and visualization of biological sequences

Cited by 834 publications

References 4 publications

The C terminus of Pcf11 forms a novel zinc-finger structure that plays an essential role in mRNA 3′-end processing

The C terminus of Pcf11 forms a novel zinc-finger structure that plays an essential role in mRNA 3′-end processing

Structural Basis of the Recruitment of Ubiquitin-specific Protease USP15 by Spliceosome Recycling Factor SART3

Thrombin Cleavage of Inter-α-inhibitor Heavy Chain 1 Regulates Leukocyte Binding to an Inflammatory Hyaluronan Matrix

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