CHMI 2227E Biochemistry I

CHMI 2227 - E.R. Gauthier, Ph.D. 1

CHMI 2227EBiochemistry I

Proteins:- Tertiary structure


Tertiary structure


Tertiary structure Secondary structure:

Involves a single type of structure: -helix -pleated sheet

Presence of interactions between amino acids that are close together in the primary structure

Main type of interaction: H bonds.

Necessary but not sufficient to make a functional protein.

Tertiary structure: Involves the folding, in space, of the whole

polypeptide chain;

Involves several elements of seconday structures, whichy interact together through different interaction forces/bonds:

H bonds Electrostatic interactions Van der Waals interactions Hydrophobic interactions Disulfide-bonds

Absolutely required for a protein to be active.

Two main types of tertiary structures exist: Fibrous (e.g. collagen) Globular (e.g. myoglobin)

myoglobin

Collagen


Tertiary structureInteraction forces For proteins in an

aqueous environment: Hydrophobic amino acids

are buried in the interior of the structure;

Hydrophilic amino acids are exposed to the solvent;

Conversely, membrane-bound proteins are exposed to an hydrophobic environment: Hydrophobic amino acids

are exposed; Hydrophilic amino acids

are buried inside.

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Check this one out: http://www.elmhurst.edu/~chm/vchembook/567tertprotein.html


Tertiary structure Protein folding occurs in specific

steps: Some individual elements of

secondary structure are first formed;

A few elements of secondary structure cluster together to form conserved folding motifs;

These bundles of secondary structure then form domains, which fold independently of the rest of the protein;

Finally, several domains interact to form the final, functional 3-D structure of the protein.

Any given protein will always adopt the same functional 3-D structure. A B


Tertiary structureFolding motifs - 1


Tertiary structureFolding motifs - 2


Tertiary structureProtein domains – Pyruvate kinase

Domain 1

Domain 2

Domain 3


Tertiary structure1. Myoglobin

Found in muscles

Binds the oxygen required for aerobic metabolism;

Associated with a heme group, which is actually responsible for binding oxygen;

-turn

-turn

Proline


Tertiary structure1. Myoglobin

Cross-sectional view

Hydrophilic amino acids: BlueHydrophobic amino acids: Yellow


Tertiary structure2. Porin – a membrane-bound protein

Hydrophilic amino acids: BlueHydrophobic amino acids: Yellow


Tertiary structureChaperones For some proteins, folding requires the help of other proteins called

chaperones;

Chaperones generally work by binding to exposed hydrophobic patches on the unfolded protein, preventing aggregation and irreversible inactivation.


Tertiary structureProtein denaturation Proteins can be

denatured by treatments that destroy the interaction forces required for the adoption of the proper 3-D structure: Heat pH Solvent Urea/guadinium: breaks up

H-bonds -ME

Check this one out: http://www.elmhurst.edu/~chm/vchembook/568denaturation.html


Tertiary structureProtein denaturation

The fact that ribonuclease can be reversibly denatured and renatured in vitro shows that the information required for the proper folding of a protein resides in its primary structure.


Examples of proteins1. Green fluorescent protein

Protein found in the jelly fish;

Has the unique property to emit a green light;

Different variants were produced by genetic engineering to produce red, yellow, cyan, blue light.

Extremely useful in cell biology: one can tag it to her/his protein of interest and follow the protein in the cell using fluorescence microscopy.



Light!



Golgi apparatusNucleus




Examples of proteins2. Prion proteins

Normal form = PrPc

Toxic form = PrPsc

http://en.wikipedia.org/wiki/Image:Prion.gif


Examples of proteins2. Prion proteins

Fiber aggregation


Important web site:http://www.pdb.org/pdb/home/home.do

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CHMI 2227E Biochemistry I