TAILIEUCHUNG - Harper’s Illustrated Biochemistry Twenty-Eighth Edition_2

The authors and publisher are pleased to present the twentyeighth edition of Harper’s Illustrated Biochemistry. This edition features for the first time multiple color images, many entirely new, that vividly emphasize the ever-increasing complexity of biochemical knowledge. The cover picture of green fluorescent protein (GFP), which recognizes the award of the 2008 Nobel Prize in Chemistry to Martin Chalfie, Roger Y. Tsien, and Osamu Shimomura, reflects the book’s emphasis on new developments. Together with its derivatives, GFP fulfills an ever-widening role in tracking protein movement in intact cells and tissues, and has multiple applications to cell biology, biochemistry and medicine. In this edition, we bid a regretful farewell to long-time author and editor,. | CHAPTER Intracellular Traffic Sorting of Proteins Robert K. Murray MD PhD 46 BIOMEDICAL IMPORTANCE Proteins must travel from polyribosomes where they are synthesized to many different sites in the cell to perform their particular functions. Some are destined to be components of specific organelles others for the cytosol or for export and yet others will be located in the various cellular membranes. Thus there is considerable intracellular traffic of proteins. A major insight was the recognition by Blobel and others that for proteins to attain their proper locations they generally contain information a signal or coding sequence that targets them appropriately. Once a number of the signals were defined see Table 46-1 it became apparent that certain diseases result from mutations that affect these signals. In this chapter we discuss the intracellular traffic of proteins and their sorting and briefly consider some of the disorders that result when abnormalities occur. MANY PROTEINS ARE TARGETED BY SIGNAL SEQUENCES TO THEIR CORRECT destinations The protein biosynthetic pathways in cells can be considered to be one large sorting system. Many proteins carry signals usually but not always specific sequences of amino acids that direct them to their destination thus ensuring that they will end up in the appropriate membrane or cell compartment these signals are a fundamental component of the sorting system. Usually the signal sequences are recognized and interact with complementary areas of other proteins that serve as receptors for those containing the signals. A major sorting decision is made early in protein biosynthesis when specific proteins are synthesized either on free or on membrane-bound polyribosomes. This results in two sorting branches called the cytosolic branch and the rough endoplasmic reticulum RER branch Figure 46-1 . This sorting occurs because proteins synthesized on membranebound polyribosomes contain a signal peptide that mediates their attachment to .

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