3HBW

Crystal Structure of Human Fibroblast Growth Factor Homologous Factor 2A (FHF2A), also referred to as Fibroblast Growth Factor 13A (FGF13A)

Summary for 3HBW

• Entry DOI: 10.2210/pdb3hbw/pdb
• Related: 1Q1U
• Descriptor: Fibroblast growth factor 13 (2 entities in total)
• Functional Keywords: beta-trefoil fold, alternative splicing, growth factor, polymorphism, hormone
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 43685.74

Authors

Mohammadi, M. (deposition date: 2009-05-05, release date: 2009-05-26, Last modification date: 2023-09-06)

Primary citation

Goetz, R.,Dover, K.,Laezza, F.,Shtraizent, N.,Huang, X.,Tchetchik, D.,Eliseenkova, A.V.,Xu, C.F.,Neubert, T.A.,Ornitz, D.M.,Goldfarb, M.,Mohammadi, M.
Crystal structure of a fibroblast growth factor homologous factor (FHF) defines a conserved surface on FHFs for binding and modulation of voltage-gated sodium channels.
J.Biol.Chem., 284:17883-17896, 2009

PubMed Abstract: Voltage-gated sodium channels (Nav) produce sodium currents that underlie the initiation and propagation of action potentials in nerve and muscle cells. Fibroblast growth factor homologous factors (FHFs) bind to the intracellular C-terminal region of the Nav alpha subunit to modulate fast inactivation of the channel. In this study we solved the crystal structure of a 149-residue-long fragment of human FHF2A which unveils the structural features of the homology core domain of all 10 human FHF isoforms. Through analysis of crystal packing contacts and site-directed mutagenesis experiments we identified a conserved surface on the FHF core domain that mediates channel binding in vitro and in vivo. Mutations at this channel binding surface impaired the ability of FHFs to co-localize with Navs at the axon initial segment of hippocampal neurons. The mutations also disabled FHF modulation of voltage-dependent fast inactivation of sodium channels in neuronal cells. Based on our data, we propose that FHFs constitute auxiliary subunits for Navs.

PubMed: 19406745
DOI: 10.1074/jbc.M109.001842

Experimental method

X-RAY DIFFRACTION (1.9 Å)