Disease relevance of ECs4313

• Interaction of E. coli Ffh/4.5S ribonucleoprotein and FtsY mimics that of mammalian signal recognition particle and its receptor [1].
• We propose that the activation is mediated to a large extent by contacts between the GTPase domains of the mycoplasma Ffh and FtsY proteins and that the contribution of the M domain and SRP RNA in the activation mechanism is mainly for modifying the conformation of the MmFfh GTPase domain [2].
• Neisseria gonorrhoeae PilA is an FtsY homolog [3].
• Comparative study of the N-terminal hydrophilic region in Streptomyces lividans and E. coli FtsY [4].
• We have determined conditions for RNA-independent association of the 'NG' GTPase domains of the prokaryotic homologs of the SRP components, Ffh and FtsY, from Thermus aquaticus [5].

High impact information on ECs4313

• These properties mimic those of mammalian SRP and its receptor, suggesting that the E. coli Ffh/4.5S ribonucleoprotein and FtsY have functions in protein targeting that are similar to those of their mammalian counterparts [1].
• The Escherichia coli guanosine triphosphate (GTP)-binding proteins Ffh and FtsY have been proposed to catalyze the cotranslational targeting of proteins to the bacterial plasma membrane [6].
• Thus, nucleotide triphosphate hydrolysis by Ffh and FtsY is likely to occur in reciprocally coupled reactions in which the two interacting guanosine triphosphatases act as regulatory proteins for each other [6].
• A mutation was introduced into the GTP-binding domain of FtsY that altered its nucleotide specificity from GTP to xanthosine triphosphate (XTP) [6].
• Importantly, the SecY translocon provides the second binding site, to which FtsY binds to form a carbonate-resistant 400-kD FtsY-SecY translocon complex [7].

Chemical compound and disease context of ECs4313

• To examine the relationship between the unusual regulation and unique architecture of the SRP pathway GTPases, we mutated an invariant glycine in Escherichia coli SRP54 and SRalpha orthologs ('Ffh' and 'FtsY', respectively) that resides at the N-GTPase domain interface [8].
• FtsY binds to the Escherichia coli inner membrane via interactions with phosphatidylethanolamine and membrane proteins [9].

Biological context of ECs4313

• Depletion of FtsY is shown to cause the accumulation of the precursor form of beta-lactamase, OmpF and ribose binding protein in vivo, whereas the processing of various other presecretory proteins is unaffected [10].
• The kinetics of interaction of FtsY with guanine nucleotides are quantitatively different from those of other GTPases [11].
• FtsY, the prokaryotic signal recognition particle receptor homologue, is essential for biogenesis of membrane proteins [12].
• Unexpectedly, despite this variance, E. coli contains essential genes encoding Ffh and FtsY with a significant similarity to proteins of the eukaryotic SRP machinery [12].
• The FtsY protein exhibits sequence homology with the SR alpha protein of eukaryotes which is involved in protein secretion [13].

Anatomical context of ECs4313

• However, the nature of the early contact of ribosomes with the membrane, and the involvement of FtsY in this interaction are unknown [14].
• The SRP receptor FtsY, GTP and inner membranes are required for release of the nascent proteins from the SRP [15].
• Functional interaction of chloroplast SRP/FtsY with the ALB3 translocase in thylakoids: substrate not required [16].
• In this study we have investigated the function of E. coli FtsY which shares sequence similarity with the alpha-subunit of the eukaryotic SRP receptor ('docking protein') in the membrane of the endoplasmic reticulum [10].
• In contrast to SRalpha, FtsY is partly membrane associated and partly located in the cytosol [17].

Associations of ECs4313 with chemical compounds

• The intrinsic guanine nucleotide dissociation rates of FtsY are about 10(5) times higher than in Ras, but similar to those seen in GTPases in the presence of an exchange factor [11].
• In the absence of phosphatidylethanolamine, the trypsin-sensitive component is sufficient for binding and function of FtsY in the targeting of membrane proteins [9].
• We have studied the binding of GTP/GDP to FtsY as well as the SRP-FtsY complex formation by monitoring the fluorescence of tryptophan 343 in the I box of mutant FtsY [18].

Analytical, diagnostic and therapeutic context of ECs4313

• Although FtsE and FtsX have been identified using SDS-PAGE, the FtsY protein has not [13].
• Expression, crystallization and preliminary X-ray diffraction study of FtsY, the docking protein of the signal recognition particle of E. coli [19].

References