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PROTEIN PHYSICS LECTURE 13-16. - Structures of water-soluble globular proteins - Physical selection of protein structures - Structural classification of proteins. Globular proteins (water-soluble). Membrane. Fibrous. H-bonds & hydrophobics. ____.  single- domain

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PROTEIN PHYSICS LECTURE 13-16

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PROTEIN PHYSICS

LECTURE 13-16

- Structures of water-soluble globular proteins

- Physical selection of protein structures

- Structural classification of proteins


Globular proteins (water-soluble)

Membrane

Fibrous

H-bonds & hydrophobics

____


 single-domain

globular protein

domain 1 domain 2

fold stack


X-RAY

One protein, various

crystallizations

NMR

Structures, compatible

with one NMR experiment

Homologous

(closely related)

proteins

Secondary structures (a-helices, b-strands) are

the most rigid and conserved details of proteins;

they are determined with the smallest errors and

form a basis of protein classification


Hemo-

globin

Hemo-

globin

Homologous proteins have similar folds.

True, but trivial.

NON-trivial:

Many NON-homologous proteins have similar folds.


-sheets: usually, twisted

(usually, right-) 

-proteins

____

H-bonds: within sheets

Hydrophobics: between sheets


sandwiches

&

cylinders

Orthogonal packing Aligned packing

of -sheets of -sheets


Retinol-binding protein

orthogonal packing

of one rolled -sheet


5

5

4

4

2’

3

5’

6

5’

3

2’

6

1

1

2

2

Trypsin-like SER-protease Acid-protease

orthogonal packings of -sheets


2

5

Greek key 2::5

Greek key 3::6

4

7

6

3

non-crossed loops

1

IG-fold:aligned packing of -sheets


-sandwich

Greek key:

edge of sandwich

Interlocked pairs:

center of sandwich

Hydrophobic surfaces

of sheets of the sandwich


1

2

2

6

6

3

5

8

6

1

8

1

3

3

8

g-crystallin bCAB cpSTNV

aligned packings

of -sheets

a) different: only topologies

b) equal: even topology


aligned packing

of -sheets

6-bladed propeller

neuraminidase


Left-handed -prism:Acyl transferase

Right-handed -prism:Pectate lyase

___________________________________________

TOPOLOGY of chain turns between parallel -strands

UNusual

LEFT-HANDED

chain turns

(AND NO

b-TWIST!)

Usual

RIGHT-HANDED

chain turns

(AND RIGHT

b-TWIST!)


-proteins

H-bonds: within helices

&

Hydrophobics: between helices


Quasi-cylindrical core (in fibrous)

Quasi-flat core

Quasi-spherical core

MOST COMMON


Orthogonal packingSimilar to orthogonal

of LONG -helicespackingof -sheets


Aligned packingSimilar to aligned

of LONG -helicespackingof -sheets


Quasi-

spherical

core:

MOST COMMON

Quasi-spherical

polyhedra

no loop turns of ~360o

no loop crossings


CLOSE PACKING

Packing of ridges:

“0-4” & “0-4”: -500

“0-4” & “1-4”: +200

-600  -500 +600  +200

IDEAL POLYHEDRA

* *


/ proteins

H-bonds: within helices & sheets

Hydrophobics: between helices & sheets


TIM barrel Rossmann fold


Regular secondary structure sequence:

b -a - b -a - b -a - b -a - b - ...

aand b layers right-handed

superhelices


Classification of

b-barrels:

“share number” S

and

strand number N.

Here: S=8, N=8

Standard

active site

position is

given by

the archi-

tecture

N

N

N

N


+ proteins

H-bonds: within helices & sheets

Hydrophobics: between helices & sheets


+:

a) A kind of regularity in the secondary

structure sequence:

b -a - b - b -a - b ...

Ferridoxin

fold


+:

b) Secondary structure sequence:

composed of irregular blocks, e.g.:

b - b - b - b - b -a - b - b -a -a ...

1

4

5

OB-fold

of the b-subdomain of nuclease

3

2

1’

Nuclease fold (“Russian doll effect”)


TYPICAL

FOLDING PATTERNS

J.Richardson, 1977


EMPIRICAL RULES

separateaand b layers right-handed

superhelices

Lost H-bonds: defect!

no large, ~360o turns

no loop crossings

NO ‘defects’


RESULT:

NARROW SET

OF PREDOMINANT FOLDING PATTERNS

these are those that have no ‘defects’


C

A

T

H

S

C

O

P

Globular

domains


Efimov’s “trees”


80/20 LAW:


EMPIRICAL RULES for FREQUENT FOLDS

aand bstructures, right-handed

separate a and b layers superhelices

Lost H-bonds: defect!

no loop crossing

no large (360-degree) turns


e.g.:

Unusual fold

(noa, almost nobstructure: bad for stability) -

BUT: very special sequence

(very many Cysteins, and therefore

very many S-S bonds)


Unusual

fold (GFP):

helix inside

Usual folds:

helices outside


What is more usual:

sequence providingainside orb binside?

a

b b

N>150


____

_____


Small

protein

details

Example:

Miller,

Janin,

Chothia

1984


WHAT IS “TEMPERATURE”?

THEORY

Closed

system:

energy

E = const

S ~ln[M]

CONSIDER: 1 state of “small part” with  & all

states of thermostat with E-. M(E-) = 1•Mth(E-)

St(E-) = k •ln[Mt(E-)]  St(E) - •(dSt/dE)|E

Mt(E-) = exp[St(E)/k] • exp[-•(dSt/dE)|E/k]

Thus: d[ln(Mt)]/dE = 1/kT


Protein structure is stable,

if its free energy is below some threshold

For example:

below that of completely unfolded chain;

or:

below that of any other globular structure


“Multitude principle”

for physical selection of folds

of globular proteins (now: “designability”):

the more sequences fit the given

architecture without destroying its stability,

the higher the occurrence of this

architecture in natural proteins.


RATIONAL STRUCTURAL CLASSIFICATION OF PROTEINS

Globular

domains

C

A

T

H

S

C

O

P


- Structures of water-soluble globular proteins

- Physical selection of protein structures: min. of defects!

- Rational structural classification of proteins


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