THE BETA-SUBUNIT OF THE SIGNAL RECOGNITION PARTICLE RECEPTOR IS A TRANSMEMBRANE GTPASE THAT ANCHORS THE ALPHA-SUBUNIT, A PERIPHERAL MEMBRANE GTPASE, TO THE ENDOPLASMIC-RETICULUM MEMBRANE
Jd. Miller et al., THE BETA-SUBUNIT OF THE SIGNAL RECOGNITION PARTICLE RECEPTOR IS A TRANSMEMBRANE GTPASE THAT ANCHORS THE ALPHA-SUBUNIT, A PERIPHERAL MEMBRANE GTPASE, TO THE ENDOPLASMIC-RETICULUM MEMBRANE, The Journal of cell biology, 128(3), 1995, pp. 273-282
The signal recognition particle receptor (SR) is required for the cotr
anslational targeting of both secretory and membrane proteins to the e
ndoplasmic reticulum (ER) membrane. During targeting, the SR interacts
with the signal recognition particle (SRP) which is bound to the sign
al sequence of the nascent protein chain. This interaction catalyzes t
he GTP-dependent transfer of the nascent chain from SRP to the protein
translocation apparatus in the ER membrane. The SR is a heterodimeric
protein comprised of a 69-kD subunit (SR alpha) and a 30-kD subunit (
SR beta) which are associated with the ER membrane in an unknown manne
r. SR alpha and the 54-kD subunit of SRP (SRP54) each contain related
GTPase domains which are required for SR and SRP function. Molecular c
loning and sequencing of a cDNA encoding SR beta revealed that SR beta
is a transmembrane protein and, like SR alpha and SRP54, is a member
of the GTPase superfamily. Although SR beta defines its own GTPase sub
family, it is distantly related to ARF and Sari. Using UV cross-linkin
g, we confirm that SR beta binds GTP specifically. Proteolytic digesti
on experiments show that SR alpha is required for the interaction of S
RP with SR. SR alpha appears to be peripherally associated with the ER
membrane, and we suggest that SR beta, as an integral membrane protei
n, mediates the membrane association of SR alpha. The discovery of its
guanine nucleotide-binding domain, however, makes it likely that its
role is more complex than that of a passive anchor for SR alpha. These
findings suggest that a cascade of three directly interacting GTPases
functions during protein targeting to the ER membrane.