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

doi:10.7554/eLife.39772

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

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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.

Original language	English (US)
Article number	e39772
Journal	eLife
Volume	7
DOIs	https://doi.org/10.7554/eLife.39772
State	Published - Oct 2018

ASJC Scopus subject areas

Neuroscience(all)
Immunology and Microbiology(all)
Biochemistry, Genetics and Molecular Biology(all)

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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.",

author = "Juan Feng and Xianchi Dong and Jennifer Pinello and Jun Zhang and Chafen Lu and Iacob, {Roxana E.} and Engen, {John R.} and Snell, {William J.} and Springer, {Timothy A.}",

note = "Funding Information: Supported by NIH grants R01-CA31798 to TAS, R01-GM56778 and R35-GM122565 to WJS, and a research collaboration with the Waters Corporation (JRE). We thank Prof. Thomas Wales for helpful discussions on the HDX experiments and Margaret Nielsen for illustrations. Publisher Copyright: {\textcopyright} Feng et al.",

year = "2018",

month = oct,

doi = "10.7554/eLife.39772",

language = "English (US)",

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journal = "eLife",

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T1 - Fusion surface structure, function, and dynamics of gamete fusogen HAP2

AU - Feng, Juan

AU - Dong, Xianchi

AU - Pinello, Jennifer

AU - Zhang, Jun

AU - Lu, Chafen

AU - Iacob, Roxana E.

AU - Engen, John R.

AU - Snell, William J.

AU - Springer, Timothy A.

N1 - Funding Information: Supported by NIH grants R01-CA31798 to TAS, R01-GM56778 and R35-GM122565 to WJS, and a research collaboration with the Waters Corporation (JRE). We thank Prof. Thomas Wales for helpful discussions on the HDX experiments and Margaret Nielsen for illustrations. Publisher Copyright: © Feng et al.

PY - 2018/10

Y1 - 2018/10

N2 - 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.

AB - 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.

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

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