RNA Pol IV and Pol V

i. Homology modeling

a) Methods is the Rosetta program, formulated by David Baker. To satisfy the program’s computational needs, a volunteer network of ∼100,000 computers, known as Rosetta@home, provides the 500,000 or so hours of processing time required to generate a structure.

ii. Structural genomics

b) which seeks to determine the X-ray structures of all representative domains, is aimed at expanding this predictive technique. The identification of structural homology is likely to provide clues as to a protein’s function even with imperfect structure prediction.

iii. Threading

c) Is a computational technique that attempts to determine the unknown structure of a protein by ascertaining whether it is consistent with a known protein structure. It does so by placing the unknown protein’s residues along the backbone of a known protein structure and then determining whether the amino acid side chains of the unknown protein are stable in that arrangement

iv. Ab initio

d) Aligns the sequence of interest with the sequence of a homologous protein or domain of known structure—compensating for amino acid substitutions, insertions, and deletions—through modeling and energy minimization calculations.

Disease

Protein or precursor involved in disease

1. Cystic fibrosis

a. Prion protein

2. Creutzfeldt–Jakob disease

b. CFTR

3. Familial hypercholesterolaemia

c. LDL receptor

4. fatal familial insomnia

d. β-amyloid protein

5. Alzheimer’s disease

e. β-hexosaminidase

lysosomal protein degradation pathways

         Found in

1. Nonselective

a-well-nourished cells

i-containing the pentapeptide Lys-Phe-Glu-Arg-Gln

2- Selective

b-starving cells

A. Destabilizing N-terminal residues Asp, Arg, Leu, Lys, and Phe have half-lives of

i. Only 2 to 3 minutes,

B. Stabilizing N-terminal residues Ala, Gly, Met, Ser, Thr, and Val have half-lives of

ii. >10 hours in prokaryotes

iii. >20 hours in eukaryotes.