5OW4

Crystal structure of a protease-resistant fragment of the Trypanosoma cruzi gamete fusion protein HAP2 ectodomain

Summary for 5OW4

• Entry DOI: 10.2210/pdb5ow4/pdb
• Descriptor: Uncharacterized protein (2 entities in total)
• Functional Keywords: gamete fusion protein, class ii fold, hap2, membrane fusion, membrane protein
• Biological source: Trypanosoma cruzi strain CL Brener
• Total number of polymer chains: 1
• Total formula weight: 64553.97

Authors

Fedry, J.,Rey, F.A.,Krey, T. (deposition date: 2017-08-30, release date: 2018-08-22, Last modification date: 2024-11-13)

Primary citation

Fedry, J.,Forcina, J.,Legrand, P.,Pehau-Arnaudet, G.,Haouz, A.,Johnson, M.,Rey, F.A.,Krey, T.
Evolutionary diversification of the HAP2 membrane insertion motifs to drive gamete fusion across eukaryotes.
PLoS Biol., 16:e2006357-e2006357, 2018

PubMed Abstract: HAPLESS2 (HAP2) is a broadly conserved, gamete-expressed transmembrane protein that was shown recently to be structurally homologous to viral class II fusion proteins, which initiate fusion with host cells via insertion of fusion loops into the host membrane. However, the functional conformation of the HAP2 fusion loops has remained unknown, as the reported X-ray structure of Chlamydomonas reinhardtii HAP2 lacked this critical region. Here, we report a structure-guided alignment that reveals diversification of the proposed HAP2 fusion loops. Representative crystal structures show that in flowering plants, HAP2 has a single prominent fusion loop projecting an amphipathic helix at its apex, while in trypanosomes, three small nonpolar loops of HAP2 are poised to interact with the target membrane. A detailed structure-function analysis of the Arabidopsis HAP2 amphipathic fusion helix defines key residues that are essential for membrane insertion and for gamete fusion. Our study suggests that HAP2 may have evolved multiple modes of membrane insertion to accommodate the diversity of membrane environments it has encountered during eukaryotic evolution.

PubMed: 30102690
DOI: 10.1371/journal.pbio.2006357

Experimental method

X-RAY DIFFRACTION (3.1 Å)