Crystal structure of human endothelial overexpressed lipopolysaccharide-associated factor 1

Abstract

Endothelial-overexpressed LPS-associated factor 1 (EOLA1) is a novel gene discovered in an effort to identify genes expressed in endothelial cells by activation of lipopolysaccharide. Previous study demonstrates that knocking down EOLA1 stimulated interleukin-6 (IL6) and apoptosis in the treatment of LPS in human umbilical vein endothelial cells (HUVEC). Analysis of the sequence of EOLA1, revealed that it has ASCH (activating signal cointegrator-1 homology) domain containing a unique β-barrel fold similar to pseudouridine synthase and archaeosine transglycosylase (PUA) domain. Because PUA domain is an ancient RNA binding domain, both ASCH and PUA domain appear to have arisen from a common RNA binding precursor. Here, I report the crystal structure of EOLA1 at 1.7 Å resolution by single wavelength anomalous dispersion (SAD) method using selenomethionine derivative crystals to solve the phasing problem. I demonstrated that EOLA1 could bind with RNA through gel mobility shift assay. Based on these results, I propose that EOLA1 is a RNA binding domain and would play regulatory roles in transcription or in protection of HUVEC injury with inflammation.