Ran dependent mechanism for nuclear export of cargo proteins containing a leucine-rich nuclear-export signal (NES).

TLS Online TPP Program

#Id: 5890

#Unit 3. Fundamental Processes

In DNA polymerase, the nucleotide-binding pocket cannot accommodate a 2’-OH on the in-coming nucleotide. This space is occupied by two amino acids that make van der Waals contacts with the sugar ring. Changing these amino acids to other amino acids with 

TLS Online TPP Program

#Id: 5891

#Unit 3. Fundamental Processes

DNA binds in a large cleft composed of three domains. The “palm” domain has important conserved sequence motifs that provide the catalytic active site. The “fingers” are involved in positioning the template correctly at the active site. The “thumb” binds the DNA as it exits the enzyme, and is important in processivity.

TLS Online TPP Program

#Id: 5892

#Unit 3. Fundamental Processes

DNA polymerases fall into five families based on sequence homologies; the palm is well conserved among them, but the thumb and fingers provide analogous secondary structure elements from different sequences.

TLS Online TPP Program

#Id: 5893

#Unit 3. Fundamental Processes

base pairs at the 3’ end of the primer, which are in the more open A-form. A sharp turn in the DNA exposes the template base to the incoming nucleotide

TLS Online TPP Program

#Id: 5894

#Unit 3. Fundamental Processes

When a nucleotide binds, the fingers domain rotates 60° toward the palm, with the tops of the fingers moving by 30 Å. The thumb domain also rotates toward the palm by 8°. 

These changes are cyclical:

They are reversed when the nucleotide is incorporated into the DNA chain, which then translocates through the enzyme to recreate an empty site.

TLS Online TPP Program

#Id: 5895

#Unit 3. Fundamental Processes

The palm domain is composed of a b sheet and contains the primary elements of the catalytic site. In particular, this region of DNA polymerase binds two divalent metal ions.