Proteins are chains of amino acids;

For example, The N-terminal end of the Rho protein is...

Serine-Serine-Glycine-Alanine-Alanine-Serine-Glycine-etc.

Attached together by their -NH2 and -COOH groups:
= their amino groups and their carboxylic acid groups

Usually hundreds, sometimes thousands of amino acids, in a particular protein molecule.

GUESS what is meant by the N-terminal end of a protein: (& what is meant by the C-terminal end!)
Amino-terminal and carboxy-terminal ends are synonyms for N and C terminal

Proteins spontaneously fold into a particular 3-D shape
which is often a rounded blob, (hemoglobin, enzymes)
but can be long & thin, as in collagen

Each kind of protein has its own proper shape, which is caused by its amino acid sequence.

Mutations, sometimes only of one amino acid, can cause this shape to be different,
or cause the shape to be unstable.
Sickle-Cell Anemia results from one amino acid substitution!

Rules for predicting folded shape from amino acid sequences

a) Non-charged side chains go together in the inside.
b) Charged side chains go on the outside
c) -NH hydrogen bonding to 0=C- groups
d) Prolines cause sharp bends, especially if next to glycine
e) Cysteines can form sulfur-sulfur bonds with each other.

Substituting a negatively-charged amino acid for a positively charged one usually has LESS effect.
Adding or removing prolines tends to have BIG effects.

First Set of Questions:

1) How many amino acids in an average protein?

2) How many different kinds of amino acids in proteins?

3) What are the names of the two ends of proteins?

*4) In principle, could these two ends form a chemical bond to each other? Hint: yes How?

5) Do the amino acids of a protein just stretch out in a long row, or does the chain bend, or what?

6) Does some kind of machinery come along and fold up the protein in a certain way, or what?

7) What are some of the rules for predicting the folding pattern of a particular protein, if you know the aa sequence?

8) Can a folding pattern be destabilized or even changed by only one change in the amino acid sequence?

9) What substitutions cause the biggest changes?

10) Can one protein sometimes fold into two alternative shapes = folding patterns?

**11) Imagine that there were certain proteins that

a) normally fold to a certain shape X
b) can very rarely fold to a different shape Y
c) once they have re-folded to Y, make you sick!
d) Y-folded proteins stimulate re-folding of X to Y

12) Would you expect genetic (inheritable) differences in susceptibility to such a disease? Hint: sure! How?

*13) Would you expect cancer could be caused by one amino acid substitution in one kind of protein?

(Yes; as many as a fifth of all human cancers seem to be caused by one particular amino acid in a protein named "ras" used in control of cell growth.)

back to syllabus