Functional Design of Proteins

(Lodish et al., 2000, Section 3.4, 3.2 )

The structural features of Insulin.

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

Location
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).
These membrane-spanning segments exist as alpha-helices (Fig. 3.34) 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)
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).
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).

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).
Hydrophobic interactions drive the initial folding of proteins (Fig. 3.14).
Some proteins need assistance in choosing the proper folding pathway. These are assisted by a group of proteins called chaperones (Fig. 3.15).
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).

Life of a protein
Proteins are degraded when they are found to improperly folded, and therefore, inactive (Fig. 3.18).
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).
Others are secreted out of the cell such as the immunoglobulins (Fig. 3.21).
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).
Some are deposited in storage tissues such as in fruits and vegatables.
Many are used as proteins (To be discussed next period).

Activity

Quiz

References:
Lodish, H., Berk, A., Zipursky, S.L., Matsudaira, P., Baltimore, D., Darnell, J., 2000, Molecular Cell Biology, 4th Ed., W.H. Freeman and Company, NY, New York. ISBN 0-7167-3136-3.