2lcz

Structural highlights

2lcz is a 1 chain structure with sequence from Zaire ebolavirus. Full experimental information is available from OCA.
Related: 2lcy
Activity: Glucokinase, with EC number 2.7.1.2

Publication Abstract from PubMed

Ebolavirus (Ebov), an enveloped virus of the family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates. The viral glycoprotein (GP) is solely responsible for virus-host membrane fusion, but how it does so remains elusive. Fusion occurs after virions reach an endosomal compartment where GP is proteolytically primed by cathepsins. Fusion by primed GP is governed by an internal fusion loop found in GP2, the fusion subunit. This fusion loop contains a stretch of hydrophobic residues, some of which have been shown to be critical for GP-mediated infection. Here we present liposome fusion data and NMR structures for a complete (54-residue) disulfide-bonded internal fusion loop (Ebov FL) in a membrane mimetic. The Ebov FL induced rapid fusion of liposomes of varying compositions at pH values at or below 5.5. Consistently, circular dichroism experiments indicated that the alpha-helical content of the Ebov FL in the presence of either lipid-mimetic micelles or small liposomes increases in samples exposed to pH </=5.5. NMR structures in dodecylphosphocholine micelles at pH 7.0 and 5.5 revealed a conformational change from a relatively flat extended loop structure at pH 7.0 to a structure with an approximately 90 degrees bend at pH 5.5. Induction of the bend at low pH reorients and compacts the hydrophobic patch at the tip of the FL. We propose that these changes facilitate disruption of lipids at the site of virus-host cell membrane contact and, hence, initiate Ebov fusion.

Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2.,Gregory SM, Harada E, Liang B, Delos SE, White JM, Tamm LK Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11211-6. Epub 2011 Jun 20. PMID:21690393^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

1. ↑ Gregory SM, Harada E, Liang B, Delos SE, White JM, Tamm LK. Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2. Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11211-6. Epub 2011 Jun 20. PMID:21690393 doi:10.1073/pnas.1104760108