Family of G-Proteins : Survey in Genomes, Structural Comparisons and Modelling(ptA)

Abstract

A protein being assigned to a family does not immediately imply that it will function as a typical member of that family. It only suggests that the protein can be associated with the family based on sequence similarity. To gain insights into the function or biological role of a protein, one must perform in-depth sequence analysis, including conserved residues required for function, sub-cellular localization, and predicted structural features.

Classification of G-proteins in Saccharomyces cerevisiae Genome Small GTP-binding proteins

Ras: 3

Ran: 2

Rho: 7

Arf: 9

Rab: 14

Elongation factor family

EF-Tu: 9

EF-Tu / IF-2: 2

EF-Tu / EFG_C: 6

Large GTP-binding proteins

Dynamin: 2

Dynamin/Dyn2/GED: 2

GBP: 0

Key Observations Gene products were identified and classified as members of the G-protein family.

The elongation factor family is the most ubiquitous, present in all prokaryotes and eukaryotes.

The presence of small GTP-binding proteins in prokaryotes is unexpected and has not been reported previously.

Large GTP-binding proteins are absent in prokaryotes.

In eukaryotes, Ras and G proteins are consistently present.

Surveys of and subunits of heterotrimeric G-proteins suggest that subunits are shared across complexes, as the number of G subunits exceeds that of G subunits in worm, fruit fly, and yeast.

Dynamin is present in all eukaryotes analyzed, but GBP is absent.

Structural Insights Some gene products assigned to G-protein subfamilies are longer or shorter than expected.

Longer proteins may contain additional domains.

Shorter proteins may require re-examination of the ORF for possible extensions, or they may represent novel members.

Future work aims to use 3D structural constraints to identify distantly related proteins.

Comparison of G-protein structures bound to GDP vs. GTP shows conformational changes, particularly in the Switch regions.

Switch II undergoes greater structural change than Switch I.

Example: G i varies by only 0.28 Å in Switch I, while EF-Tu varies up to 6.72 Å.

Conclusion The important deduction is that homologous G-protein structures differ in their conformations to varying extents in the Switch regions, depending on whether GDP or GTP is bound. This must be carefully considered in 3D modeling of G-proteins, as using multiple homologous structures as templates can complicate accurate modeling.