Fusion surface structure, function, and dynamics of gamete fusogen HAP2
Juan Feng,
Xianchi Dong,
Jennifer Pinello,
Jun Zhang,
Chafen Lu,
Roxana E Iacob,
John R Engen,
William J Snell,
Timothy A Springer
Affiliations
Juan Feng
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States; Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, United States
Xianchi Dong
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States; Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, United States
Jennifer Pinello
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
Jun Zhang
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
Chafen Lu
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States; Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, United States
Roxana E Iacob
Department of Chemistry and Chemical Biology, Northeastern University, Boston, United States
John R Engen
Department of Chemistry and Chemical Biology, Northeastern University, Boston, United States
William J Snell
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States; Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, United States
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.
