Melnick J, Dul J L, Argon Y
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Nature. 1994 Aug 4;370(6488):373-5. doi: 10.1038/370373a0.
During their transit through the endoplasmic reticulum, newly synthesized light and heavy chains of immunoglobulins associate with two endoplasmic reticulum stress proteins. BiP/GRP78, a member of the HSP70 family, binds these polypeptides, presumably through promiscuously exposed hydrophobic sequences, soon after their translocation into the endoplasmic reticulum. GRP94, another endoplasmic reticulum stress protein homologous to HSP90, also associates with unassembled immunoglobulin chains, but its interaction is biochemically, kinetically and structurally distinct from BiP's. We report here that whereas BiP preferentially binds an early disulphide intermediate of light chain and dissociates within a few minutes, GRP94 exclusively binds fully oxidized molecules and dissociates with a half-time of 50 min. These results indicate that GRP94 is itself a chaperone which acts after BiP.
在免疫球蛋白新合成的轻链和重链通过内质网的过程中，它们会与两种内质网应激蛋白结合。HSP70家族成员BiP/GRP78在这些多肽转运到内质网后不久，大概通过随机暴露的疏水序列与它们结合。GRP94是另一种与HSP90同源的内质网应激蛋白，也会与未组装的免疫球蛋白链结合，但其相互作用在生化、动力学和结构上与BiP的不同。我们在此报告，BiP优先结合轻链的早期二硫键中间体并在几分钟内解离，而GRP94只结合完全氧化的分子，解离半衰期为50分钟。这些结果表明，GRP94本身就是一种伴侣蛋白，在BiP之后发挥作用。
