100,558 research outputs found
ERp44 mediates a thiol-independent retention of formylglycine-generating enzyme in the endoplasmic reticulum
No full textMariappan M, Radhakrishnan K, Dierks T, Schmidt B, von Figura K. ERp44 mediates a thiol-independent retention of formylglycine-generating enzyme in the endoplasmic reticulum. JOURNAL OF BIOLOGICAL CHEMISTRY. 2008;283(10):6375-6383.Inside the endoplasmic reticulum (ER) formylglycine-generating enzyme (FGE) catalyzes in newly synthesized sulfatases the post-translational oxidation of a specific cysteine. Thereby formylglycine is generated, which is essential for sulfatase activity. Here we show that ERp44 interacts with FGE forming heterodimeric and, to a lesser extent, also heterotetrameric and octameric complexes, which are stabilized through disulfide bonding between cysteine 29 of ERp44 and cysteines 50 and 52 in the N-terminal region of FGE. ERp44 mediates FGE retrieval to the ER via its C-terminal RDEL signal. Increasing ERp44 levels by overexpression enhances and decreasing ERp44 levels by silencing reduces ER retention of FGE. Suppressing disulfide bonding by mutating the critical cysteines neither abrogates ERp44.FGE complex formation nor interferes with ERp44-mediated retention of FGE, indicating that noncovalent interactions between ERp44 and FGE are sufficient to mediate ER retention. The N-terminal region of FGE harboring Cys(50) and Cys(52) is dispensible for catalytic activity in vitro but required for FGE-mediated activation of sulfatases in vivo. This in vivo activity is affected neither by overexpression nor by silencing of ERp44, indicating that a further ER component interacting with the N-terminal extension of FGE is critical for sulfatase activation
The non-catalytic N-terminal extension of formylglycine-generating enzyme is required for its biological activity and retention in the endoplasmic reticulum
No full textMariappan M, Gande SL, Radhakrishnan K, Schmidt B, Dierks T, von Figura K. The non-catalytic N-terminal extension of formylglycine-generating enzyme is required for its biological activity and retention in the endoplasmic reticulum. JOURNAL OF BIOLOGICAL CHEMISTRY. 2008;283(17):11556-11564.Formylglycine-generating enzyme (FGE) catalyzes the oxidation of a specific cysteine residue in nascent sulfatase polypeptides to formylglycine (FGly). This FGly is part of the active site of all sulfatases and is required for their catalytic activity. Here we demonstrate that residues 34-68 constitute an N-terminal extension of the FGE catalytic core that is dispensable for in vitro enzymatic activity of FGE but is required for its in vivo activity in the endoplasmic reticulum (ER), i.e. for generation of FGly residues in nascent sulfatases. In addition, this extension is needed for the retention of FGE in the ER. Fusing a KDEL retention signal to the C terminus of FGE is sufficient to mediate retention of an N-terminally truncated FGE but not sufficient to restore its biological activity. Fusion of FGE residues 1-88 to secretory proteins resulted in ER retention of the fusion protein. Moreover, when fused to the paralog of FGE (pFGE), which itself lacks FGly-generating activity, the FGE extension ( residues 34-88) of this hybrid construct led to partial restoration of the biological activity of co-expressed N-terminally truncated FGE. Within the FGE N-terminal extension cysteine 52 is critical for the biological activity. We postulate that this N-terminal region of FGE mediates the interaction with an ER component to be identified and that this interaction is required for both the generation of FGly residues in nascent sulfatase polypeptides and for retention of FGE in the ER
Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India
No full textKrishnamoorthy, R., Munirathinam, A., Dhananjeyan, K.J., Hiriyan, J., Mariappan, T., Samuel, P. Philip, Venkatesh, A. (2013): Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India. Zootaxa 3701 (4): 447-459, DOI: 10.11646/zootaxa.3701.4.
Paralog of the formylglycine-generating enzyme - retention in the endoplasmic reticulum by canonical and noncanonical signals
No full textGande SL, Mariappan M, Schmidt B, Pringle TH, von Figura K, Dierks T. Paralog of the formylglycine-generating enzyme - retention in the endoplasmic reticulum by canonical and noncanonical signals. FEBS JOURNAL. 2008;275(6):1118-1130.Formylglycine-generating enzyme (FGE) catalyzes in newly synthesized sulfatases the oxidation of a specific cysteine residue to formylglycine, which is the catalytic residue required for sulfate ester hydrolysis. This post-translational modification occurs in the endoplasmic reticulum (ER), and is an essential step in the biogenesis of this enzyme family. A paralog of FGE (pFGE) also localizes to the ER. It shares many properties with FGE, but lacks formylglycine-generating activity. There is evidence that FGE and pFGE act in concert, possibly by forming complexes with sulfatases and one another. Here we show that human pFGE, but not FGE, is retained in the ER through its C-terminal tetrapeptide PGEL, a noncanonical variant of the classic KDEL ER-retention signal. Surprisingly, PGEL, although having two nonconsensus residues (PG), confers efficient ER retention when fused to a secretory protein. Inducible coexpression of pFGE at different levels in FGE-expressing cells did not significantly influence the kinetics of FGE secretion, suggesting that pFGE is not a retention factor for FGE in vivo. PGEL is accessible at the surface of the pFGE structure. It is found in 21 mammalian species with available pFGE sequences. Other species carry either canonical signals (eight mammals and 26 nonmammals) or different noncanonical variants (six mammals and six nonmammals). Among the latter, SGEL was tested and found to also confer ER retention. Although evolutionarily conserved for mammalian pFGE, the PGEL signal is found only in one further human protein entering the ER. Its consequences for KDEL receptor-mediated ER retrieval and benefit for pFGE functionality remain to be fully resolved
FIGURE 3 in Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India
No full textFIGURE 3. Legs of Toxorhynchites tyagii, sp. n.Published as part of <i>Krishnamoorthy, R., Munirathinam, A., Dhananjeyan, K.J., Hiriyan, J., Mariappan, T., Samuel, P. Philip & Venkatesh, A., 2013, Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India, pp. 447-459 in Zootaxa 3701 (4)</i> on page 452, DOI: 10.11646/zootaxa.3701.4.4, <a href="http://zenodo.org/record/10099074">http://zenodo.org/record/10099074</a>
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
FIGURE 4 in Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India
No full textFIGURE 4. Male genitalia of Toxorhynchites tyagii, sp. n. A, Dorsal aspect; B, basal mesal lobe; C, tergum IX.Published as part of <i>Krishnamoorthy, R., Munirathinam, A., Dhananjeyan, K.J., Hiriyan, J., Mariappan, T., Samuel, P. Philip & Venkatesh, A., 2013, Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India, pp. 447-459 in Zootaxa 3701 (4)</i> on page 453, DOI: 10.11646/zootaxa.3701.4.4, <a href="http://zenodo.org/record/10099074">http://zenodo.org/record/10099074</a>
FIGURE 7 in Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India
No full textFIGURE 7. Agarose gels showing the amplification of the CO1 gene of (A) Toxorhynchites tyagii, sp n. and (B) Tx. splendens.Published as part of <i>Krishnamoorthy, R., Munirathinam, A., Dhananjeyan, K.J., Hiriyan, J., Mariappan, T., Samuel, P. Philip & Venkatesh, A., 2013, Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India, pp. 447-459 in Zootaxa 3701 (4)</i> on page 457, DOI: 10.11646/zootaxa.3701.4.4, <a href="http://zenodo.org/record/10099074">http://zenodo.org/record/10099074</a>
FIGURE 1 in Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India
No full textFIGURE 1. Head and thorax of holotype female of Toxorhynchites tyagii, sp. n.Published as part of <i>Krishnamoorthy, R., Munirathinam, A., Dhananjeyan, K.J., Hiriyan, J., Mariappan, T., Samuel, P. Philip & Venkatesh, A., 2013, Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India, pp. 447-459 in Zootaxa 3701 (4)</i> on page 449, DOI: 10.11646/zootaxa.3701.4.4, <a href="http://zenodo.org/record/10099074">http://zenodo.org/record/10099074</a>
FIGURE 5 in Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India
No full textFIGURE 5. Pupa of Toxorhynchites tyagii, sp. n. A, terminal abdominal segments (dorsal); B, cephalothorax; C, metanotum.Published as part of <i>Krishnamoorthy, R., Munirathinam, A., Dhananjeyan, K.J., Hiriyan, J., Mariappan, T., Samuel, P. Philip & Venkatesh, A., 2013, Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India, pp. 447-459 in Zootaxa 3701 (4)</i> on page 454, DOI: 10.11646/zootaxa.3701.4.4, <a href="http://zenodo.org/record/10099074">http://zenodo.org/record/10099074</a>
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