Introduction to Molecular and Cell Biology, Biol. 220 Lecture 4: Protein Structure
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Four levels of structure

1. Primary Fig. 3.4a
   Fig. 3.4a Primary Amino Acid Structure of hemagglutinin

   

2. Secondary  Fig. 3.4b
   Fig. 3.4b Secondary and tertiary structure of hemagglutinin

   

• alpha-helix  Fig. 3.6, held together with H-bonds
  Fig. 3.6 Alpha-helix
  
• amphipathic  Fig. 3.7, Fig. 3.9a, attractions of hydrophobic faces
  

  Fig. 3.7 Amphipathic region of five associated alpha-helices

   
  Fig. 3.9a Interactions of two amphipathic alpha-helix

  

• beta-sheet  Fig. 3.8
• anti-parallel  Fig. 3.8
• parallel 
  
  

  Fig. 3.8 Beta-sheets

  
  
  

• loops Fig. 3.9 b, non-structural regions that connect sheets and helices
• turns
• glycine
• proline
• coils Fig. 3.8c  random coils are loose helical structures
3. Tertiary  Fig. 3.4b
4. Quaternary  Fig. 3.4c



Fig. 3.4c Quaternary structure of hemagglutinin

Additional Groups

Prosthetic groups - small molecules
    bound to proteins (zinc, iron common)  Fig. 3.9c

Fig. 3.9b Prosthetic group (Calcium) associated with loop

Fig. 3.9c Zinc finger

Functional Design of Proteins

Let's look at the structural features of Insulin.

What determines how and where a protein functions?

The structure of the polypeptide chains determines the location, function, modification, and lifetime of each protein.

Location

Hydrophobicity is one of the major forces in the initial folding of proteins.

Protein will either reside in an aqueous or hydrophobic environment.

Membrane proteins can be classified into two broad categories, integral and peripheral, based on the nature of the protein-membrane interactions.

• Integral membrane proteins, also called intrinsic proteins, have one or more segments that are embedded in the phospholipid bilayer of the membrane. (Fig. 3.33).
  Fig. 3.33 Glycophorin A
  
  
• These membrane-spanning segments can exist either as alpha-helices (Fig. 3.34)
  Fig. 3.34  Bacteriorhodopsin
  
  or multiple beta-strands (Fig. 3.35) and contain hydrophobic amino acids that interact with the hydrophobic fatty acyl groups of the membrane phospholipids. Note that hydrophilic residues tend to group together in the hydrophobic environment (Fig. 3.33)
  Fig. 3.35  OmpF, a porin found in the outer membrane of E. coli.
  
  
• Some integral membrane proteins do not actually span the phospholipid bilayer but are covalently attached to fatty acids that are embedded in the membrane (Fig. 3.36).
  Fig. 3.36  Integral proteins.
  
  
• Peripheral membrane proteins do not span the phospholipid bilayer but instead are bound to the membrane indirectly by interactions with integral membrane proteins or directly by interactions with the polar head groups of phospholipids (Fig. 3.32).
  Fig. 3.32  Typical eukaryotic membrane.
  
  

Structure and Function Relationships

The tertiary/quaternary structures of proteins influences their ability to function properly.

• Proper folding is necessary and since improperly folded protein are targeted for degredation (Fig. 3.13).
  Fig. 3.13  Protein denaturation and renaturation.
  
  
• Hydrophobic interactions drive the initial folding of proteins (Fig. 3.14).
  Fig. 3.14  Unassisted protein folding.
  
  
• Some proteins need assistance in choosing the proper folding pathway.  These are assisted by a group of proteins called chaperones (Fig. 3.15).
  Fig. 3.15  Chaperone mediated folding (a) and the two states of the chaperone GroEL (b left tight, substrate bound) (b right relaxed, substrate released).
  
  
• Some proteins require modification, such as the addition of a methyl, acetyl, phosphate, fatty acid, or glycosyl groups, before they are fully active.
  
• Some enzymes bind to prosthetic groups (Fig 3.11).
  Fig. 3.11  Myoblobin (top) and Hemoglobin (bottom) both carry prosthetic groups which help bind oxygen.
  
  

Life of a protein

Proteins are degraded when they are found to improperly folded, and therefore, inactive (Fig. 3.18).
Fig. 3.18  Protein degredation pathway (a) and the proteosome complex (b).


Some proteins have special sequences that are target for rapid degradation:

RxxLGxIGN
PEST
N-terminal ends that contain R, K, F, L, or W

Types of Protein Function

Some proteins are membrane bound such as the nuclear pore complex which directs trafic into and out of the nucleus (Fig. 3.20a).
Fig. 3.20a  Nuclear pore complex.

Others are secreted out of the cell such as the immunoglobulins (Fig. 3.21).
Fig. 3.21  Antibody molecule (immunoglobulin).

Some serve as regulators that bind to either nucleic acid sequences or other proteins.

Some serve as signal transducers in complex signaling pathways (Fig. 3.34).
Fig. 3.34  Bacteriorhodopsin

Some are deposited in storage tissues such as in fruits and vegatables.

Many are used as enzymes (To be discussed next period).  

Activity

Quiz

Created 2004 by CA Rinehart• email CA Rinehart

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