Data Protein Bank Structure (www.rcsb.org)
Early Structures
lysozyme myoglobin
Carboxypeptidase Serine protease
Proteins have recurring folding patterns.
The classical protein folding patterns Antiparallel a Parallel a/b Antiparallel b
(also, a+b)
Antiparallel a: 4-helix bundle
Hydrophobic interior
Note the "packing angle" between helices
Amino acid side chains
Polypeptide backbone
a-helix
3.6 residues/turn =>5.4 helical repeat 1.5 rise/residue
~10 packing diameter
a-helix side view
Top view: a residue every 100 ("helical wheel" construct)
rior
N W
inte
Y K
C E V D K A V
Pro
tein
L
Sequence from one helix of 4-helix bundle: AKNVDYCKEWLV
Myohemerythrin helix
Poly-Ala
"Tight packing" of hydrophobic side chains gives rise to helix packing angle of ~20.
Larger a-helical domain-Note that not all packing angles are ~20.
Armadillo repeats of b-catenin (Weis lab, Stanford)--lotsa a
Parallel a/b domains
Hydrophobic interior
Parallel beta strands
"dipeptide repeat" ~6.5
~4.75
~6.5
The twist of the parallel b sheet is due to the intrinsic right-handed twist of the polypeptide backbone.
Close packing of hydrophobic side chains results in preferred angles of packing of helices on parallel beta sheets.
C
N
Antiparallel b domains
Antiparallel b sheets
~7.0
"dipeptide repeat" ~7.0
How much diversity in secondary structure?
Ramachandran Plots
Non-glycine
Glycine
"Tight turns" are common connections between b strands
Type I' turns, residue 2 is always glycine Type II' turns, residue 1 is always glycine.
In addition to a helices, 310 helices are occasionally found in proteins
310 helix
a helix
(3.613 helix)
he lix
10
3
a
he lix
Antiparallel a
Parallel a/b
Antiparallel b
(also, a+b)
Unusual a/b structure: RNase inhibitor
Kobe & Deisenhofer, Nature 366:751 (1993)
Protein Domains
Antiparallel b
a/b barrel
Triose Phosphate Isomerase (TIM)
Parallel a/b
Pyruvate Kinase One domain Three domains
(plus an N-terminal bit)
Pathogenic Pathway of Bacterial Exotoxins
(e.g. Pseudomonas aeruginosa A)
Receptor exotoxin binding
Internalization-enzymatic domain gets into cytoplasm.
Toxic activity (e.g. ADPribosylation of polypeptide elongation factor EF2)
Pathogenic Pathway of Bacterial Exotoxins
(e.g. Pseudomonas aeruginosa exotoxin A)
Receptor binding
Internalization-enzymatic domain gets into cytoplasm.
Toxic activity (e.g. ADPribosylation of polypeptide elongation factor EF2)
?
? ?
Toxin
Pseudomonas exotoxin A
Subunits/MW
Single polypeptide 66 kDa
Function
ADP-ribosylation of EF-2 =>Inhibit protein synthesis ADP-ribosylation of EF-2 =>Inhibit protein synthesis ADP-ribosylation of Gn N- glycosidase; removes single adenine from 28S RNA of 60S ribosome ADP-ribosylation of GI
Diphtheria toxin
Single polypeptide 58 kDa
Cholera toxin & E. coli heat- labile toxin (LT) Shiga toxin; E. coli verotoxins
AB5 A = 27; B= 11.6 kDa AB5
Pertussis toxin
S 1 S 2 S 3 2S 4 S 5 S 1 = 26.2 kDa S 2 = 21.9 S 3 = 21.9 S 4 = 12.1 S 5 = 11.8
Diphtheria Toxin
Diphtheria Toxin
Pseudomonas Toxin
ADPR-transferase Diphtheria Receptor binding Pseudomonas
Mem. Transloc.
Receptor binding
Mem. Transloc.
ADPR-transferase
Diphtheria and Pseudomonas toxins have similar ADPR-transferase domains (low but significant seq. identity), but other domains are differ...