The Signal Recognition Particle Receptor Is a Complex That Contains Two Distinct Polypeptide Chains

Signal recognition particle (SRP) and SRP receptor are known to be essential components of the cellular machinery that targets nascent secretory proteins to the endoplasmic reticulum (ER) membrane. Here we report that the SRP receptor contains, in addition to the previously identified and sequenced 69-kD polypeptide (α-subunit, SRα), a 30-kD β-subunit (SRβ). When SRP receptor was purified by SRP-Sepharose affinity chromatography, we observed the co-purification of two other ER membrane proteins. Both proteins are ∼30 kD in size and are immunologically distinct from each other, as well as from SRα and SRP proteins. One of the 30-kD proteins (SRβ) forms a tight complex with SRα in detergent solution that is stable to high salt and can be immunoprecipitated with antibodies to either SRα or SRβ. Both subunits are present in the ER membrane in equimolar amounts and co-fractionate in constant stoichiometry when rough and smooth liver microsomes are separated on sucrose gradients. We therefore conclude that SRβ is an integral component of SRP receptor. The presence of SRβ was previously masked by proteolytic breakdown products of SRα observed by others and by the presence of another 30-kD ER membrane protein (mp30) which co-purifies with SRα. Mp30 binds to SRP-Sepharose directly and is present in the ER membrane in several-fold molar excess of SRα and SRβ. The affinity of mp30 for SRP suggests that it may serve a yet unknown function in protein translocation.