Crystal Structure of Human EOLA1 Implies Its Possibility of RNA Binding
Human endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1) has been suggested to regulate inflammatory responses in endothelial cells by controlling expression of proteins, interleukin-6 and vascular cell adhesion molecule-1, and by preventing apoptosis. To elucidate the structur...
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doaj-2ce03250932f4fde821e05315583e65d2020-11-25T01:58:27ZengMDPI AGMolecules1420-30492019-09-012419352910.3390/molecules24193529molecules24193529Crystal Structure of Human EOLA1 Implies Its Possibility of RNA BindingMinju Kim0Sang Ho Park1Joon Sung Park2Hyun-Jung Kim3Byung Woo Han4Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, KoreaResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, KoreaResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, KoreaCollege of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, KoreaResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, KoreaHuman endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1) has been suggested to regulate inflammatory responses in endothelial cells by controlling expression of proteins, interleukin-6 and vascular cell adhesion molecule-1, and by preventing apoptosis. To elucidate the structural basis of the EOLA1 function, we determined its crystal structure at 1.71 Å resolution and found that EOLA1 is structurally similar to an activating signal cointegrator-1 homology (ASCH) domain with a characteristic β-barrel fold surrounded by α-helices. Despite its low sequence identity with other ASCH domains, EOLA1 retains a conserved ‘<b>G</b>x<b>K</b>xx<b>E</b>x<b>R</b>’ motif in its cavity structure. The cavity harbors aromatic and polar residues, which are speculated to accommodate nucleotide molecules as do YT521-B homology (YTH) proteins. Additionally, EOLA1 exhibits a positively charged cleft, similar to those observed in YTH proteins and the ASCH protein from <i>Zymomonas</i> <i>mobilis</i> that exerts ribonuclease activity. This implies that the positively charged cleft in EOLA1 could stabilize the binding of RNA molecules. Taken together, we suggest that EOLA1 controls protein expression through RNA binding to play protective roles against endothelial cell injuries resulting from lipopolysaccharide (LPS)-induced inflammation responses.https://www.mdpi.com/1420-3049/24/19/3529activating signal cointegrator-1 homology (asch) domainendothelial-overexpressed lipopolysaccharide-associated factor 1 (eola1)lipopolysaccharide (lps)rna-binding domain |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Minju Kim Sang Ho Park Joon Sung Park Hyun-Jung Kim Byung Woo Han |
spellingShingle |
Minju Kim Sang Ho Park Joon Sung Park Hyun-Jung Kim Byung Woo Han Crystal Structure of Human EOLA1 Implies Its Possibility of RNA Binding Molecules activating signal cointegrator-1 homology (asch) domain endothelial-overexpressed lipopolysaccharide-associated factor 1 (eola1) lipopolysaccharide (lps) rna-binding domain |
author_facet |
Minju Kim Sang Ho Park Joon Sung Park Hyun-Jung Kim Byung Woo Han |
author_sort |
Minju Kim |
title |
Crystal Structure of Human EOLA1 Implies Its Possibility of RNA Binding |
title_short |
Crystal Structure of Human EOLA1 Implies Its Possibility of RNA Binding |
title_full |
Crystal Structure of Human EOLA1 Implies Its Possibility of RNA Binding |
title_fullStr |
Crystal Structure of Human EOLA1 Implies Its Possibility of RNA Binding |
title_full_unstemmed |
Crystal Structure of Human EOLA1 Implies Its Possibility of RNA Binding |
title_sort |
crystal structure of human eola1 implies its possibility of rna binding |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2019-09-01 |
description |
Human endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1) has been suggested to regulate inflammatory responses in endothelial cells by controlling expression of proteins, interleukin-6 and vascular cell adhesion molecule-1, and by preventing apoptosis. To elucidate the structural basis of the EOLA1 function, we determined its crystal structure at 1.71 Å resolution and found that EOLA1 is structurally similar to an activating signal cointegrator-1 homology (ASCH) domain with a characteristic β-barrel fold surrounded by α-helices. Despite its low sequence identity with other ASCH domains, EOLA1 retains a conserved ‘<b>G</b>x<b>K</b>xx<b>E</b>x<b>R</b>’ motif in its cavity structure. The cavity harbors aromatic and polar residues, which are speculated to accommodate nucleotide molecules as do YT521-B homology (YTH) proteins. Additionally, EOLA1 exhibits a positively charged cleft, similar to those observed in YTH proteins and the ASCH protein from <i>Zymomonas</i> <i>mobilis</i> that exerts ribonuclease activity. This implies that the positively charged cleft in EOLA1 could stabilize the binding of RNA molecules. Taken together, we suggest that EOLA1 controls protein expression through RNA binding to play protective roles against endothelial cell injuries resulting from lipopolysaccharide (LPS)-induced inflammation responses. |
topic |
activating signal cointegrator-1 homology (asch) domain endothelial-overexpressed lipopolysaccharide-associated factor 1 (eola1) lipopolysaccharide (lps) rna-binding domain |
url |
https://www.mdpi.com/1420-3049/24/19/3529 |
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