Protein Functions and Evolution: An Overview of Protein Domains and DNA Transcription, Study notes of Inorganic Chemistry

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Bioinorganic Chemistry

CHEM-

Protein Shape and Protein Shape and

Function Function

DNA Transcription DNA Transcription

1 7 7 Protein Functions Protein Functions

Functions Functions

• (^) Catalysis (enzymes)
• (^) Binding and transport (active/passive)
  • (^) Protein-DNA/RNA binding histones, transcription factors
  • (^) Protein-protein interactions antibodies, lysozymes
  • (^) Protein-fatty acid binding apolipoproteins lipid transport in lymph and blood
  • (^) Protein – small molecules drug interaction and transport

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Protein functions are so varied that

they are difficult to categorize.

Example: Example:

 -crystallin-crystallin: eye lens protein – needs

to stay stable and transparent for a

lifetime (very little turnover in the

eye lens)

Protein Functions Protein Functions

1 7 7 Protein Functions Protein Functions

1 7 7 How do proteins evolve? How do proteins evolve? By addition of domainsdomains at either end of protein sequence or at loop sites [see next slides]. Often through gene duplication followed by divergence. Multi-domain proteins are a result of gene fusion, where multiple genes end up in a single Open Reading Frame of protein coding. Repetitions of the same domain in a single protein occur frequently, this results from gene duplication followed by gene fusion. Protein Functions Protein Functions

1 7 7 Protein structure Protein structure modification modification Insertion/deletion of secondary structural elements can ‘easily’ be done at loop sites. These sites are normally at the surface of a protein Protein Modifications Protein Modifications

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Chymotryps

in

“Modern” 2-barrel

structure

Putative ancestral barrel structure Active site (combination of ancestral active site residues) Activity 1000-10,000 times enhanced Protein structure modification Protein structure modification Protein Modifications Protein Modifications Active site coupling

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The basic functional unit of a

protein is a domain:

• (^) Compact, semi-independent unit

(Richardson, 1981).

• (^) Stable unit of a protein structure

that can fold autonomously

(Wetlaufer, 1973).

• (^) Recurring functional and

evolutionary modules (Bork,

Protein Domains Protein Domains Protein Modifications Protein Modifications

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Pyruvate kinase Pyruvate kinase (ADP(ADPATP)ATP)

Phosphotransferase, contains a manganese io  barrel regulatory domain  barrel catalytic substrate binding domain  nucleotide binding domain Domains can be continuous or discontinuous. Protein Domains Protein Domains

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Complex protein functions are a result of multiple Complex protein functions are a result of multiple

domains, and often synergistic domains. domains, and often synergistic domains.

An example is the so-called swivelling domain in pyruvate phosphate dikinase (Herzberg et al., 1996), which brings an intermediate enzymatic product over about 45 Å from the active site of one domain to that of another. This enhances the enzymatic activity: delivery of intermediate product not by a diffusion process but by active transport dramatically improves enzymatic rates. Protein Domains Protein Domains

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DNA DNA

Transcription Transcription

1 7 7 Molecular Visualization of Molecular Visualization of DNA DNA DNA Replication, DNA Transcription into RNA RNA translation into Proteins http://www.youtube.com/watch?v=4PKjF7OumYo

1 7 7 DNA Transcription DNA Transcription There are three known types RNA Pol I synthesizes r RNA RNA Pol II synthesizes formation of m RNA RNA Pol III synthesizes t RNA and other small RNA RNA polymerases do not work alone, they need the help of regularors such as promoters and enhancers. They also need several transcription factors. RNA Polymerases (RNA RNA Polymerases (RNA Pol) Pol)

1 7 7 DNA Transcription DNA Transcription The transcription process has many control mechanisms. Protein-DNA interactions play a central role in these mechanisms. DNA itself has regulator sitesregulator sites called promoters promoters and enhancersenhancers. There are also smaller proteins called transcription factorstranscription factors that regulate the transcription process. Transcription Regulators Transcription Regulators