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the cell membrane.The signal hypothesis of G. Blobel, a 1999 Nobel laureate, and his colleagues, explains the mechanism for membrane attachment. The mechanism applies to both prokaryotes and eukaryotes. Here, we describe it in mammals. The signal for membrane insertion is coded into the first one to three dozen amino acids of membranebound proteins. This signal peptide takes part in a chain of events that leads the ribosome to attach to the membrane and to the insertion of the protein.The rst step occurs when the signal peptide becomes accessible outside of the ribosome.A ribonucleoprotein particle called the signal recognition particle (SRP), which consists of six different proteins and a 7S RNA about three hundred nucleotides long, recognizes the signal peptide. The complex of signal recognition particle, ribosome, and signal peptide then passes, or diffuses, to a membrane, where the SRP binds to a receptor called a docking protein (DP) or signal recognition particle receptor ( g. 11.25). During this time, protein synthesis halts. The ribosome is brought into direct contact with the membrane, and other proteins of the membrane help anchor the ribosome. Protein synthesis then resumes, with the nascent protein usually passing directly into a translocation channel (translocon). Once through the membrane, the signal peptide is cleaved from the protein by an enzyme called signal peptidase. A striking veri cation of this hypothesis came about through recombinant DNA techniques (chapter 13).A signal sequence was placed in front of the -globin gene, whose protein product is normally not transported through a membrane. When this gene was translated, the ribosome became membrane bound, and the protein passed through the membrane. Since different proteins enter different membranebound compartments (e.g., the Golgi apparatus), some mechanism must direct a nascent protein to its proper

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(626)

The McGraw Hill Companies, 2001

arctan( CR))

(627)

Folded polypeptide (a) (c)

1 2a = (1 2a )2 = 1

H (j ) = 90 arctan( CR) You can verify by inspection that the amplitude response of the high-pass lter will be zero at = 0 and will asymptotically approach 1 as approaches in nity, while the phase shift is 90 at = 0 and tends to zero for increasing Amplitudeand-phase response curves for the high-pass lter are shown in Figure 617 These plots have been normalized to have the lter cutoff frequency 0 = 1 rad/s Note that, once again, it is possible to de ne a cutoff frequency at 0 = 1/RC in the same way as was done for the low-pass lter

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1 Phase, degrees 10 1 10 0 101 102 103 Radian frequency (logarithmic scale) 104 08 Amplitude 06 04 02 0 10 2 80 60 40 20 0 10 2 10 1 10 0 101 102 103 Radian frequency (logarithmic scale) 104

Figure 11.27 The change in structure of GroEL with GroES attached explains how the chaperonin can unfold a partially folded polypeptide to allow it to refold in a different way. (a) A space- lling model of GroEL is shown without (left) and with (right) GroES. GroEL s rings are blue and magenta, and GroES is green. (b) The same structures are seen in a cutaway view. (c) This diagram shows how the attachment of GroES causes the top part of the top ring of GroEL to pull apart an improperly folded polypeptide. ([a & b]: Reprinted from Bernd Bakau

Compute the response of the RC lter in the circuit of Figure 616 Evaluate the response of the lter at = 2 100 and 2 10,000 rad/s

and Arthur L. Horwich, The Hsp70 and Hsp60 Chaperone Machines in Cell,

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Find: The frequency response, HV (j ) Assumptions: None Analysis: We rst recognize that the cutoff frequency of the high-pass lter is 0 = 1/RC = 2 4,000 rad/s Next, we write the frequency response as in equation 625: Vo j CR 0 HV (j ) = = arctan (j ) = Vi 1 + j CR 2 0 2 1+ 0

This part of the expansion is very small as compared to the original value So the equation can be expressed as d = R R 1 2 ( f R ) sin d = R R (1 2 ( f R ) sin )

= 0025 1546

vol. 92, 351 366. Copyright 1988, with permission from Elsevier Science.)

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