High impact information on Histidyl-aspartyl-glutamyl-leucine

• Sorting of these proteins is dependent on a C-terminal tetrapeptide signal, usually Lys-Asp-Glu-Leu (KDEL in the single letter code) in animal cells, His-Asp-Glu-Leu (HDEL) in Saccharomyces cerevisiae [1].
• The ERD2 gene, which encodes the yeast HDEL (His-Asp-Glu-Leu) receptor, is essential for growth (Semenza, J. C., K. G. Hardwick, N. Dean, and H. R. B. Pelham. 1990. Cell. 61:1349-1357; Lewis, M. J., D. J. Sweet, and H. R. B. Pelham. 1990. Cell. 61:1359-1363) [2].
• The HDEL sequence of Sec20p is not essential for viability but helps to maintain intracellular levels of the protein [3].
• The gene products of all the cloned members of this family contain a carboxy-terminal His-Asp-Glu-Leu peptide that may form the signal for retention in the endoplasmic reticulum [4].
• Electrophysiological studies using 80K-H mutants showed that three domains of 80K-H (the two EF-hand structures, the highly acidic glutamic stretch, and the His-Asp-Glu-Leu sequence) are critical determinants for TRPV5 activity [5].

Biological context of Histidyl-aspartyl-glutamyl-leucine

• The endoplasmic reticulum calcium-binding protein of 55 kDa is a novel EF-hand protein retained in the endoplasmic reticulum by a carboxyl-terminal His-Asp-Glu-Leu motif [6].
• A mutant protein lacking the HDEL sequence produced by in vitro mutagenesis has been shown to be secreted into medium in transient expression assays [7].
• In dividing root-tip cells of Pinus brutia Ten., immunolocalization of the luminal endoplasmic reticulum (ER) proteins, which have the C-terminal HDEL sequence, reveals that the ER is reorganized during the preprophase/prophase stage [8].
• Since the beta-subunit, which contains a C-terminal His-Asp-Glu-Leu (HDEL) motif, may function to link the catalytic subunit to the KDEL receptor as a retrieval mechanism, we sought to map the regions of the mouse beta-subunit protein responsible for mediating the association with the alpha-subunit [9].

Gene context of Histidyl-aspartyl-glutamyl-leucine

• Reticulocalbin, a novel endoplasmic reticulum resident Ca(2+)-binding protein with multiple EF-hand motifs and a carboxyl-terminal HDEL sequence [7].
• The carboxyl-terminal sequence His-Asp-Glu-Leu (HDEL) is required for retention of ERC-55 in the ER [6].
• A mutant Kex2 enzyme with a C-terminal HDEL sequence releases correctly folded human insulin-like growth factor-1 from a precursor accumulated in the yeast endoplasmic reticulum [10].
• In the work presented, we have constructed an expression vector (pSGNH2) for the secretion of protein disulfide isomerase (PDI; EC 5.3.4.1) from Aspergillus niger, in which the retention signal His-Asp-Glu-Leu (H-D-E-L) was modified to Ala-Leu-Glu-Gln (A-L-E-Q) via the polymerase chain reaction (PCR) method [11].

Analytical, diagnostic and therapeutic context of Histidyl-aspartyl-glutamyl-leucine

• His-Asp-Glu-Leu (HDEL)-bearing proteins were quantified in different endoplasmic reticulum (ER) subcompartments of Saccharomyces cerevisiae and the plant parasite Uromyces viciae-fabae by immuno-electron microscopy (immuno-EM) [12].

References