BiP maintains the permeability barrier of the ER membrane by sealing the lumenal end of the translocon pore before and early in translocation.
Secretory proteins are cotranslationally translocated across the mammalian ER membrane through an aqueous pore in the translocon while the permeability barrier is maintained by a tight ribosome-membrane junction. The lumenal end of the pore is also blocked early in translocation. Extraction of soluble lumenal proteins from microsomes and reconstitution with purified proteins demonstrate, by fluorescence collisional quenching, that BiP seals the lumenal end of this pore. BiP also seals translocons that are assembled but are not engaged in translocation. These ribosome-free translocons have smaller pores (9-15 A diameter versus 40-60 A in functioning translocons) and are generated when ribosomes dissociate from functioning translocons with large pores. BiP therefore maintains the permeability barrier by sealing both nontranslocating and newly targeted translocons.
Hamman
B D
BD
Department of Medical Biochemistry and Genetics, Texas A&M University, College Station 77843-1114, USA.
Hendershot
L M
LM
Johnson
A E
AE
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002458:Cell Fractionation; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007454:Iodides / Q000493:pharmacokinetics; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008861:Microsomes / Q000737:chemistry / Q000378:metabolism; D009243:NAD / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000502:physiology; D011817:Rabbits; D012270:Ribosomes / Q000378:metabolism; D012995:Solubility; D014867:Water / Q000378:metabolism; D015003:Yeasts / Q000737:chemistry / Q000378:metabolism
D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D007454:Iodides; C060153:KAR2 protein, yeast; D008565:Membrane Proteins; D012333:RNA, Messenger; D014867:Water; D009243:NAD; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate