Enhancement of membrane insertion and function in a type IIIb membrane protein following introduction of a cleavable signal peptide.
The human beta 2 adrenergic receptor is a type IIIb membrane protein. It has a putative seven-transmembrane topology but lacks an amino-terminal cleavable signal sequence. The mechanism by which the amino terminus of the beta 2 receptor is translocated across the endoplasmic reticulum membrane is unknown. Furthermore, it is not known if translocation as a type IIIb protein is essential for the proper folding. Our studies indicate that conversion of beta 2 receptor from a type IIIb to a type IIIa membrane protein by introducing an NH2-terminal cleavable signal sequence enhances translocation of the receptor into the endoplasmic reticulum membrane, thereby facilitating expression of functional receptor.
Guan
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XM
Howard Hughes Medical Institute, Department of Molecular and Cellular Physiology, Stanford University, California 94305.
Kobilka
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TS
Kobilka
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BK
D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D002474:Cell-Free System; D004082:Dihydroalprenolol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
D008565:Membrane Proteins; D021382:Protein Sorting Signals; D011943:Receptors, Adrenergic, beta; D011994:Recombinant Proteins; D004082:Dihydroalprenolol