Please answer ALL parts to this question. Thank you! The protein CDC42 is import

Question

Please answer ALL parts to this question. Thank you!

The protein CDC42 is important for progression of the cell division cycle. This link shows the amino acid sequence of a specific form of CDC42 encoded in human cells:

Go to this website for the cDNA sequence >http://www.ncbi.nlm.nih.gov/nuccore/89903011    Scroll to the bottom and find the nucleotide sequence of the cDNA encoding this protein, and several dozen lines above it locate the translation (predicted amino acid sequence) of CDC42. By convention, the base sequence is printed in a 5’ to 3’ direction, and the amino acid sequence is printed in an N-terminal to C-terminal direction.

A) Suppose you engineer a chimeric version of Ras, in which its C-terminal 20 amino acids are removed and replaced by the 20 C-terminal amino acids of CDC42. Would this chimeric protein be recognized and lipid-modified by farnesyl:protein transferase? Explain your answer briefly for full credit.

B) Suppose your colleague finds new experimental evidence that CDC42 is a target of a kinase called BTK. For information on this kinase, see: http://www.uniprot.org/uniprot/Q06187    How many sites of possible phosphorylation by BTK exist within CDC42? __________   

C) In the primary structure of CDC42, write the two longest regions of consecutive nonpolar amino acid side chains (not including Cys).______________________________   __________________________________

D) What does your answer to the previous question suggest regarding the likelihood that CDC42 harbors a transmembrane domain?   

Explanation / Answer

A. Farnesyl protein transferase are inhibitors of Ras depemdent proliferase activity according to the available literature. It should be known which domain of the Ras protein are the target of this inhibition by the Farnesyl transferase. The case where the C-terminal is the target, in that case the deletion of the 20 amino acids replaced by sequence of CDC42 will be affected for the inhibition by the Farnesyl transferase.

B. There is one site of tyrosine phoshorylation on CDC42 by the BTK tyrosine kinases. That is at Cdc42G12Vp.

Note: Reference:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC98957/

C. Arg186, Trp194, Phe102, Leu77, Ile177 from CDC42 form the hydrophobic pocket not including Cys. for further reference, please refer: Structure of the Rho Family GTP-Binding Protein Cdc42 in Complex with the Multifunctional Regulator RhoGDI. Hoffman, Gregory R. et al. Cell , Volume 100 , Issue 3 , 345 - 356

D. CDC42 has transmembrane domains. Along with the Rho proteins and the GDI complex it places within the membrane.

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