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Elife. 2018 Oct 3;7. pii: e39772. doi: 10.7554/eLife.39772.

Fusion surface structure, function, and dynamics of gamete fusogen HAP2.

Author information

1
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.
2
Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, United States.
3
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States.
4
Department of Chemistry and Chemical Biology, Northeastern University, Boston, United States.
#
Contributed equally

Abstract

HAP2 is a class II gamete fusogen in many eukaryotic kingdoms. A crystal structure of Chlamydomonas HAP2 shows a trimeric fusion state. Domains D1, D2.1 and D2.2 line the 3-fold axis; D3 and a stem pack against the outer surface. Surprisingly, hydrogen-deuterium exchange shows that surfaces of D1, D2.2 and D3 closest to the 3-fold axis are more dynamic than exposed surfaces. Three fusion helices in the fusion loops of each monomer expose hydrophobic residues at the trimer apex that are splayed from the 3-fold axis, leaving a solvent-filled cavity between the fusion loops in each monomer. At the base of the two fusion loops, Arg185 docks in a carbonyl cage. Comparisons to other structures, dynamics, and the greater effect on Chlamydomonas gamete fusion of mutation of axis-proximal than axis-distal fusion helices suggest that the apical portion of each monomer could tilt toward the 3-fold axis with merger of the fusion helices into a common fusion surface.

KEYWORDS:

HAP2; biochemistry; chemical biology; chlamydomonas reinhardtii; dynamics; fusion loop; molecular biophysics; structural biology

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