How does the KDEL receptor regulate protein retrieval?
ER lumen contains chaperones BiP HSPA5, Grp94 HSP90B1, PDI family, calreticulin that may leak into Golgi during non-selective bulk flow; retention therefore relies on active retrieval not static retention. Soluble residents carry C-terminal KDEL tetrapeptide Lys-Asp-Glu-Leu or variant HDEL. If they escape to cis-Golgi beyond, KDEL receptors family of seven-transmembrane proteins Erd2 in yeast KDELR1-3 in mammals concentrated in Golgi and ERGIC recognize tetrapeptide. Binding strongly pH dependent because histidine residues protonate at mildly acidic Golgi lumen pH 6.0-6.2 stabilizing interacti
Ref: Alberts et al., MBC Chapter 13: KDEL receptor pH-dependent retrieval to ER via COPI.