FGF/FGFR beta Sheet Nomenclature

by

Larry P. Taylor, Ph. D.

 

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Email: lpt

Molecular & Behavioral Neuroscience Institute

The University of Michigan

Ann Arbor, MI

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FGF Site: FGF Intro     Notes     References     FGF Sequences     FGFR Sequences

beta Sheet Nomenclature


FGF molecules share a common protein architecture: the beta trefoil (three-fold repeat of a four-stranded sheet assembly without extended alpha helix strands possessing a pseudo three-fold axis of symmetry) motif. FGF ligands typically contain 12 beta sheets arranged in 3 groups of 4 strands. The C and N terminal sheets are adjacent which serves to close and stabilize the overall structure. Heparin binding to FGF stabilizes this junction and may play a key role in regulation of this molecule. The beta sheets are numbered 1 through 12, beginning at the N terminal of the sequence. The base of the trefoil (sheets 1, 4, 5, 8, 9, & 12) form a beta barrel motif. This architecture for FGF 2 is shown in Kinemage 1.


Since Telokin has a 7 anti-parallel beta strand architecture common to immunoglobulins, it serves as a reference template for the FGFR ligand binding domains. The Telokin sheets are arranged into two primary parallel groups (of 4 and 3 strands) whose apparent wrapping around a central core has been described as a "beta barrel." The 7 sheets of Telokin are described numerically in Kinemage 2  and labeled alphabetically from A-G  in Kinemage 3. The Telokin architecture is summarized at PDB Sum.

 

The FGFR beta sheets have been mapped onto a Telokin template. This scheme, using the ligand binding domains D2 and D3 from the FGF 2-FGFR 1 dimer (Brookhaven 1CVS),  is depicted numerically in Kinemage 4 and alphabetically in Kinemage 5.


Finally, the ligand binding domain is split into three defined immunoglobulin-like regions: domains D2, the Linker (between D2 and D3) and domain D3. These are shown in Kinemage 6.

The Kinemages:

 

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  Kinemage 1: The FGF beta Sheets

View 1 the sheets identified
View 2 the molecule rotated to highlight the three distinctive folds of the trefoil architecture. This arrangement is maintained by the fold (in red) in which the two beta sheets 1 (N-terminal) and 12 (C-terminal) bring together the loose terminal ends of the protein sequence. The base of the FGF trefoil (sheets 1,4,5,8,9,& 12) form a beta barrel motif. 



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298 K

Click on KiNG to see   FGF Sheets


 Kinemage 2:  Telokin Template (Numerical)

View 1 identifies the 7 anti-parallel beta sheets as numbered sheets
View 2 an arbitrary side view
View 3 an arbitrary top view
View 4 the "vertical" view



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188 K

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 Telokin Sheets (Numerical)


Kinemage 3:  Telokin Template (Alphabetical)

Telokin is a classic representation of the immunoglobin-like "beta barrel" architecture.

 

View 1 identifies the 7 anti-parallel beta sheets as English alphabetical characters
View 2 an arbitrary side view
View 3 an arbitrary top view
View 4 the "vertical" view

 



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187 K

Click on KiNG to see Telokin Sheets (Alphabetical)


  Kinemage 4: FGFR Ligand Binding Domain beta Sheets (Numerical)

The secondary structure  of domains D2-D3 of the FGFR ligand binding domain are mapped onto a Telokin template using numerical designations.

View 1 FGFR 1 ligand binding domain
View 2 the "vertical" view

 



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395 K

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Kinemage 5: FGFR Ligand Binding Domains (Alphabetical)

The secondary structure  of domains D2-D3 of the FGFR ligand binding domain are mapped onto a Telokin template using alphabetical designations.

View 1 FGFR 1 ligand binding domain
View 2 the "vertical" view

 



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394 K

Click on KiNG to see   FGFR Sheets (Alphabetical)

 

Kinemage 6: FGFR Ligand Binding Domains

This is a simple schematic to highlight the D2, linker and D3 Domains of FGFR's.

View 1 FGF-FGFR Complex
View 2 "Vertical" view often seen in journals

 



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416 K

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Sources:


FGF 2 Coordinates were taken from Brookhaven Database file 1BFF. Telokin coordinates were taken from Brookhaven Database file 1FHG. FGFR coordinates were taken from Brookhaven Database file 1CVS.

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FGF Site: FGF Intro     Notes     References     FGF Sequences     FGFR Sequences 

My University Home    Harris Links     Chemistry / Modeling Links


Copyright 2005-2020  by Larry P. Taylor
Molecular & Behavioral Neuroscience Institute
University of Michigan

All Rights Reserved

Supported by the Pritzker Neuropsychiatric Disorders Research Consortium, and by NIH Grant 5 P01 MH42251, Conte Center Grant #L99MH60398, RO1 DA13386 and the Office of Naval Research (ONR) N00014-02-1-0879 to Huda Akil & Stanley J. Watson. at the Molecular & Behavioral Neuroscience Institute.