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Motifs and folds, contd'

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Found at the edges of a sheet, or when one side of the sheet ... Does this recapitulate evolution? the folding pathway? Domains. Proteins fold heirarchically. ... – PowerPoint PPT presentation

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Title: Motifs and folds, contd'


1
Motifs and folds, contd.
2
Proline helix C-cap
note hydrophobic cluster
structural variability
Sequence pattern...nppnnppHNYFPDEn
Pro blocks helix
D or E stabilizes tight turn
Locations of non-polar (magenta) and polar
(green) sidechains
nnon-polarppolar...alternative aas
3
Two Helix motifs
a-a corner(helix-turn-helix)
EF-hand (binds Ca2)
4
beta-strand
middle strand
edge strand
Antiparallel
Parallel
5
Sequence motifs for beta strands
Hydrophobic
Amphipathic
Note preference for beta-branched aas I,V,T
Found at the edges of a sheet, or when one side
of the sheet is exposed to solvent (i.e. 2-layer
proteins).
Found in the buried middle strands of sheets in
3-layer proteins.
6
beta hairpins
Two adjacent antiparallel beta strands a beta
hairpin Shown are tight turns, 2 residues in
the loop region (shaded). Hairpins can have as
many as 20 residues in the loop region.
7
hairpin motifs
Serine beta-hairpin (my naming). A specific
pattern (DPESG) forms an incomplete alpha-helical
turn 4-residues long.
Extended Type-1 hairpin. A type-1 tight turn
has only 2 residues in the turn. This motif, more
common than the tight turn, has an additional Pro
or polar sidechain. Pattern PDG.
8
diverging turn
Exercise Find the diverging turn in 1CSK.
Diverging turns have a Type-2 beta turn and two
strands that do not pair. The consensus sequence
pattern is PDG. The residue before G can be
anything polar, but not a D or an N.
9
Greek key motif
One of the most common arrangements of four
strands. Two permutations. 2341 and 3214
beta meander
Exercise Download 2PLT. Find the Greek key
motifs.
10
bab motif
When a helix occurs between two strands, they are
often paired in a parallel sheet.
The cross-over from one strand to the next is
almost always right-handed. It is not known why
this is true. (NOTE the cross-over is always
right-handed even when the two strands are not
paired!!)
11
TOPS diagrams
beta strand pointing up
beta strand pointing down
alpha helix
bab motif
C
N
Note R-handed crossover!
12
babab motif
1
2
3
Only 3 are possible. (with R-handed crossovers)
1
2
3
3
1
2
13
Efimovs theory
A. Efimov showed that almost all protein
structures can be classified as being one of 7
trees, each starting with a motif and growing
by one secondary structure unit at time. Does
this recapitulate evolution? the folding pathway?
14
Domains
Proteins fold heirarchically. secondary structure
--gt motifs --gt subdomains--gtdomains --gt
multidomain proteins --gt complexes
Most domains fold independently of the rest of
the chain.
15
All alpha folds
3-helix bundle 1CUK 156-203 4-helix
bundle 1NFN Globin 1DWT ...many many other
16
alpha/beta folds
TIM barrel 8TIM Rossman fold 1HET
176-318 many others...
Exercise in 1HET, find the crevice between two
babab motifs where NAD binding commonly occurs.
Exercise Draw TOPS diagram for 1HET 176-318.
17
all beta folds
Jelly roll 1JMU 371-500D,
2PLT barrels 1EMC propellers beta-helix
Exercise Draw TOPS diagrams for the two domains
above.
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