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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:

A single click on the KiNG logo will launch the appropriate kinemage. The number under the KiNG logo is the download size (in bytes).

Use the left mouse button to rotate the molecule.

If the KiNG logo is absent or the application does not launch, see Gray Box Error.

 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. 

Image requires a Java enabled browser 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

Image requires a Java enabled browser 188 K
Click on KiNG to see	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

Image requires a Java enabled browser 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

Image requires a Java enabled browser 395 K
Click on KiNG to see	FGFR Sheets (Numerical)

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

Image requires a Java enabled browser 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

Image requires a Java enabled browser 416 K
Click on KiNG to see	FGFR Domains

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     Site Map

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Copyright 2005-2007 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.