PROTEIN PHYSICS
This presentation is the property of its rightful owner.
Sponsored Links
1 / 45

PROTEIN PHYSICS LECTURE 13-16 PowerPoint PPT Presentation


  • 98 Views
  • Uploaded on
  • Presentation posted in: General

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

Download Presentation

PROTEIN PHYSICS LECTURE 13-16

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Protein physics lecture 13 16

PROTEIN PHYSICS

LECTURE 13-16

- Structures of water-soluble globular proteins

- Physical selection of protein structures

- Structural classification of proteins


Protein physics lecture 13 16

Globular proteins (water-soluble)

Membrane

Fibrous

H-bonds & hydrophobics

____


Protein physics lecture 13 16

 single-domain

globular protein

domain 1 domain 2

fold stack


Protein physics lecture 13 16

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


Protein physics lecture 13 16

Hemo-

globin

Hemo-

globin

Homologous proteins have similar folds.

True, but trivial.

NON-trivial:

Many NON-homologous proteins have similar folds.


Protein physics lecture 13 16

-sheets: usually, twisted

(usually, right-) 

-proteins

____

H-bonds: within sheets

Hydrophobics: between sheets


Protein physics lecture 13 16

sandwiches

&

cylinders

Orthogonal packing Aligned packing

of -sheets of -sheets


Protein physics lecture 13 16

Retinol-binding protein

orthogonal packing

of one rolled -sheet


Protein physics lecture 13 16

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


Protein physics lecture 13 16

2

5

Greek key 2::5

Greek key 3::6

4

7

6

3

non-crossed loops

1

IG-fold:aligned packing of -sheets


Protein physics lecture 13 16

-sandwich

Greek key:

edge of sandwich

Interlocked pairs:

center of sandwich

Hydrophobic surfaces

of sheets of the sandwich


Protein physics lecture 13 16

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


Protein physics lecture 13 16

aligned packing

of -sheets

6-bladed propeller

neuraminidase


Protein physics lecture 13 16

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!)


Protein physics lecture 13 16

-proteins

H-bonds: within helices

&

Hydrophobics: between helices


Protein physics lecture 13 16

Quasi-cylindrical core (in fibrous)

Quasi-flat core

Quasi-spherical core

MOST COMMON


Protein physics lecture 13 16

Orthogonal packingSimilar to orthogonal

of LONG -helicespackingof -sheets


Protein physics lecture 13 16

Aligned packingSimilar to aligned

of LONG -helicespackingof -sheets


Protein physics lecture 13 16

Quasi-

spherical

core:

MOST COMMON

Quasi-spherical

polyhedra

no loop turns of ~360o

no loop crossings


Protein physics lecture 13 16

CLOSE PACKING

Packing of ridges:

“0-4” & “0-4”: -500

“0-4” & “1-4”: +200

-600  -500 +600  +200

IDEAL POLYHEDRA

* *


Protein physics lecture 13 16

/ proteins

H-bonds: within helices & sheets

Hydrophobics: between helices & sheets


Protein physics lecture 13 16

TIM barrel Rossmann fold


Protein physics lecture 13 16

Regular secondary structure sequence:

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

aand b layers right-handed

superhelices


Protein physics lecture 13 16

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


Protein physics lecture 13 16

+ proteins

H-bonds: within helices & sheets

Hydrophobics: between helices & sheets


Protein physics lecture 13 16

+:

a) A kind of regularity in the secondary

structure sequence:

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

Ferridoxin

fold


Protein physics lecture 13 16

+:

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”)


Protein physics lecture 13 16

TYPICAL

FOLDING PATTERNS

J.Richardson, 1977


Protein physics lecture 13 16

EMPIRICAL RULES

separateaand b layers right-handed

superhelices

Lost H-bonds: defect!

no large, ~360o turns

no loop crossings

NO ‘defects’


Protein physics lecture 13 16

RESULT:

NARROW SET

OF PREDOMINANT FOLDING PATTERNS

these are those that have no ‘defects’


Protein physics lecture 13 16

C

A

T

H

S

C

O

P

Globular

domains


Protein physics lecture 13 16

Efimov’s “trees”


Protein physics lecture 13 16

80/20 LAW:


Protein physics lecture 13 16

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


Protein physics lecture 13 16

e.g.:

Unusual fold

(noa, almost nobstructure: bad for stability) -

BUT: very special sequence

(very many Cysteins, and therefore

very many S-S bonds)


Protein physics lecture 13 16

Unusual

fold (GFP):

helix inside

Usual folds:

helices outside


Protein physics lecture 13 16

What is more usual:

sequence providingainside orb binside?

a

b b

N>150


Protein physics lecture 13 16

____

_____


Protein physics lecture 13 16

Small

protein

details

Example:

Miller,

Janin,

Chothia

1984


Protein physics lecture 13 16

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 physics lecture 13 16

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


Protein physics lecture 13 16

“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.


Protein physics lecture 13 16

RATIONAL STRUCTURAL CLASSIFICATION OF PROTEINS

Globular

domains

C

A

T

H

S

C

O

P


Protein physics lecture 13 16

- Structures of water-soluble globular proteins

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

- Rational structural classification of proteins


  • Login