Protein Structure Lecture 2262003 beta sheets are twisted

Protein Structure Lecture 2/26/2003

beta sheets are twisted • Parallel sheets are less twisted than antiparallel and are always buried. • In contrast, antiparallel sheets can withstand greater distortions (twisting and betabulges) and greater exposure to solvent.

The twist is due to chiral (l)- amino acids in the extended plane. This chirality gives the twist and distorts Hbonding. A tug of war exists between conformational energies of the side chain and maximal Hbonding.

Two proteins exhibiting a twisting b sheet Bovine carboxypeptidase Triose phosphate isomerase

Connections between adjacent b sheets

Sheet facts • Repeat distance is 7. 0 Å • R group on the Amino acids alternate up-down-up above and below the plane of the sheet • 2 - 15 amino acids residues long • 2 - 15 strands per sheet • Ave of 6 strands with a width of 25 Å • parallel less stable than anti-parallel • Anti-parallel needs a hairpin turn • Tandem parallel needs crossover connection which has a right handed sense

Non-repetitive regions Turns - coils or loops link regions of secondary structure 50% of structure of globular proteins are not repeating structures b bends type I and type II : hairpin turn between anti parallel sheets

Reverse Turns Type I f 2 = -60 o, y 2 = -30 o f 3 = -90 o, y 3 = 0 o Type II f 2 = -60 o, y 2 = 120 o f 3 = 90 o, y 3 = 0 o

two-residue turns

Protein Structure Terminology

Folding motifs (super secondary structure) Certain amino sequences have patterns to their folding. A. bab motif, B. b hairpin C. aa motif

beta-alpha-beta • parallel beta-strands connected by longer regions containing alpha-helical segments • almost always has a right-handed fold

Helix-turn-helix • • • loop regions connecting alpha-helical segments can have important functions e. g. EF-hand DNA-binding EF hand loop ~ 12 residues polar and hydrophobic a. a. conserved positions Glycine is invariant at the sixth position The calcium ion is octahedrally coordinated by carboxyl side chains, main chain groups and bound solvent

Protein Folds There is an estimate of about 10000 different folding patterns in proteins About half of the proteins fall into a few dozen folding patterns. Those proteins related by structure are called families. A large Family are the c cytochromes (see Figure 6 -31 pg 147 in FOB. )

The b barrel has several types of structures that have been mimicked in art. A. rubredoxin B. Human prealbumin or porins C. Triose phosphate isomerase

Concanavalin A Mostly a b barrel motif

Carbonic anhydrase H 2 CO 3 - CO 2 + H 2 O

Nucleotide binding-Rossmann Fold

Glyceraldehyde-3 phosphate dehydrogenase Binding NADH in the Rossmann fold.

Zinc fingers C 2 H 2 zinc finger: It is characterized by the sequence CX 2 -4 C. . HX 2 -4 H, where C = cysteine, H = histidine, X = any amino acid. C 4 zinc finger: Its consensus sequence is CX 2 CX 13 CX 2 CX 1415 CX 9 CX 2 C. The first four cysteine residues bind to a zinc ion and the last four cysteine residues bind to another zinc ion C 6 zinc finger. It has the consensus sequence CX 2 CX 6 CX 5 -6 CX 2 CX 6 C. The yeast's Gal 4 contains such a motif where six cysteine residues interact with two zinc ions

C 2 H 2 zinc finger

Zinc Finger DNA-binding

Summary Chapter 6 • Four levels of protein structure – – • • • Primary Secondary Tertiary Quaternary Peptide bond (w bond) Sheets and helices (f and y bonds) Tertiary structure (fibrous or globular) Structure determination and fold space Protein folding discussed after kinetics -lecture 19