The glycine brace: a component of Rab, Rho, and Ran GTPases associated with hinge regions of guanine- and phosphate-binding loops.
BACKGROUND
Ras-like GTPases function as on-off switches in intracellular signalling pathways and include the Rab, Rho/Rac, Ran, Ras, Arf, Sar and G alpha families. How these families have evolutionarily diverged from each other at the sequence level provides clues to underlying mechanisms associated with their functional specialization.


RESULTS
Bayesian analysis of divergent patterns within a multiple alignment of Ras-like GTPase sequences identifies a structural component, termed here the glycine brace, as the feature that most distinguishes Rab, Rho/Rac, Ran and (to some degree) Ras family GTPases from other Ras-like GTPases. The glycine brace consists of four residues: An aromatic residue that forms a stabilizing CH-pi interaction with a conserved glycine at the start of the guanine-binding loop; a second aromatic residue, which is nearly always a tryptophan, that likewise forms stabilizing CH-pi and NH-pi interactions with a glycine at the start of the phosphate-binding P-loop; and two other residues (typically an aspartate and a serine or threonine) that, together with a conserved buried water molecule, form a network of interactions connecting the two aromatic residues.


CONCLUSIONS
It is proposed that the two glycine residues function as hinges and that the glycine brace influences guanine nucleotide binding and release by interacting with these hinges.
Neuwald
Andrew F
AF
Institute for Genome Sciences and Department of Biochemistry & Molecular Biology, University of Maryland School of Medicine, 801 West Baltimore St,, BioPark II, Baltimore, MD 21201, USA. aneuwald@som.umaryland.edu
D000595:Amino Acid Sequence; D005998:Glycine / Q000235:genetics / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism*; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D011487:Protein Conformation; D016415:Sequence Alignment; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D006150:Guanine Nucleotides; D020559:Monomeric GTP-Binding Proteins; D020691:rab GTP-Binding Proteins; D020931:ran GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D005998:Glycine