Protein Structure and Function

Course #2
Protein Structure and Function
 What is a protein?

Amino acid
20 types of amino acids
Proteins Fold Into a Conformation of Lowest Energy

Think about the

surrounding
environment : water
While some proteins need some help to refold properly
Zoom into the tertiary & quaternary structure

Quaternary structure

Tertiary structure
 Protein Molecules Serve as Subunits for
the Assembly of Large Structures

Advantages:
1. Requirement of small amount of genetic information
2. Assembly and disassembly can be controlled since the subunits associate
through multiple bonds of low energy – non-covalent bonds
3. Any errors in the synthesis of the structure can be more easily avoided
 What is a protein family?
Group of proteins that share a common
evolutionary origin, reflected by their related
functions and similarities in sequence or structure.
Homology Modeling?
 What is a protein superfamily?

The largest grouping of proteins for which common

ancestry can be inferred

Sequence similarity
Structural similarity
Mechanistic similarity
Protein Structure and Function
All Proteins Bind to Other Molecules
for Functioning Properly
How noncovalent bonds mediate interactions
between macromolecules?

Multi-enzyme complexes help to increase the rate of cell metabolism

Enzymatic acceleration of chemical reactions by
decreasing the activation energy
Regulation of Protein Function

Inhibition

Activation
 Positive Regulation

Negative Regulation
 What we learned so far?
• Amino acids differ from each other by their radical side
chains which can be hydrophobic, hydrophilic or charged.
• Definition of phi and psi angles as well as the
Ramachandran plot
• Some proteins can fold by themselves while the others need
some auxiliary proteins to fold.
• There a certain level protein organization : primary,
secondary, tertiary and quaternary
• Advantages of having similar and modular subunits to form
complex structures
• Protein family, homology modeling
• Binding site of proteins
• Advantage of having multi-enzyme complexes
• Enzymes – activation energy
• Negative and positive regulation of enzymes
• Allostery – regulation that depends on allosteric interaction
HOW CELLS READ THE GENOME :
FROM DNA TO PROTEIN
 DIFFERENCES BETWEEN DNA AND RNA

Cells produce several types of RNA:

m-RNA, t-RNA and r-RNA

 DNA is transcribed by RNA polymerase

In bacteria:
One type of RNA polymerase

In eukaryotes:
Three types of RNA polymerase: RNA polymerase I,
II and III
The transcription cycle of bacterial RNA polymerase
 Initiation of transcription of a eukaryotic gene
by RNA polymerase II

TATA
 POLYMERASE II ALSO REQUİRES ACTİVATOR,
MEDIATOR AND CHROMATİN-MODIFYING PROTEINS
TRANSCRIPTION ELONGATION PRODUCES
SUPERHELICAL TENSION IN DNA

DNA gyrase (topoisomerase)

 TRANSCRIPTION ELONGATION IN
EUKARYOTES IS TIGHTLY COUPLED TO RNA
PROCESSING
THE «RNA FACTORY» CONCEPT FOR
EUKARYOTIC RNA POLYMERASE II
 RNA SPLICING

ALTERNATIVE SPLICING
ABNORMAL PROCESSING OF THE PRIMARY
RNA TRANSCRIPT