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Title: Fusion surface structure, function, and dynamics of gamete fusogen HAP2

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.

Authors:
 [1];  [1];  [2];  [2];  [1];  [3];  [3];  [2]; ORCiD logo [1]
  1. 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
  2. Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
  3. Department of Chemistry and Chemical Biology, Northeastern University, Boston, United States
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
INDUSTRYNIH
OSTI Identifier:
1479008
Resource Type:
Journal Article
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 7; Journal Issue: 10, 2018; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Feng, Juan, Dong, Xianchi, Pinello, Jennifer, Zhang, Jun, Lu, Chafen, Iacob, Roxana E., Engen, John R., Snell, William J., and Springer, Timothy A. Fusion surface structure, function, and dynamics of gamete fusogen HAP2. United States: N. p., 2018. Web. doi:10.7554/eLife.39772.
Feng, Juan, Dong, Xianchi, Pinello, Jennifer, Zhang, Jun, Lu, Chafen, Iacob, Roxana E., Engen, John R., Snell, William J., & Springer, Timothy A. Fusion surface structure, function, and dynamics of gamete fusogen HAP2. United States. doi:10.7554/eLife.39772.
Feng, Juan, Dong, Xianchi, Pinello, Jennifer, Zhang, Jun, Lu, Chafen, Iacob, Roxana E., Engen, John R., Snell, William J., and Springer, Timothy A. Wed . "Fusion surface structure, function, and dynamics of gamete fusogen HAP2". United States. doi:10.7554/eLife.39772.
@article{osti_1479008,
title = {Fusion surface structure, function, and dynamics of gamete fusogen HAP2},
author = {Feng, Juan and Dong, Xianchi and Pinello, Jennifer and Zhang, Jun and Lu, Chafen and Iacob, Roxana E. and Engen, John R. and Snell, William J. and Springer, Timothy A.},
abstractNote = {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.},
doi = {10.7554/eLife.39772},
journal = {eLife},
issn = {2050-084X},
number = 10, 2018,
volume = 7,
place = {United States},
year = {2018},
month = {10}
}

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