How are motifs and domains formed?
Simple secondary structures combine to form structural motifs or larger functional domains
What is a Protein sequence motif?
A protein sequence motif is a pattern of amino acids found in related genes or proteins
Where can motifs and domains be identified within a proteins structure?
Motifs and Domains are independent orders of structure identified within overall tertiary structures
- found and conserved in functionally related proteins
Define what is meant by a motif?
Combination of 2 or more secondary structures to form a recognisable folded arrangement
What is the function of the greek key motif?
Associated with the formation of Β amyloid aggregates and fibrils in alzheimers
Describe what a domain is in molecular terms
Complex structure at tertiary or Quaternary level often involving interactions between distant parts of
proteins or motifs
Explain the structure of Parallel Β sheet motifs
Parallel strands of a Β sheet interlinked with an ɒ helix
=> forming an Β-ɒ-Β motif
How do α helices specifically bind to DNA?
Bind to major groove in DNA
- amino acid sequence of a DNA Binding motif provides specificity
- different DNA binding domains and motifs present the binding helix using different arrangements of the structural motif
Define domain
Functional protein folding units found across different genes and phyla
Describe the structure of beta barrels
Β sheets twisted around forming a closed circular structure
Define what a dimer is
An oligomer consisting of two monomers joined by (strong/weak, covalent/intermolecular) bonds
Describe the domains present in Phospholipase C
4 different recognisable domains present
- each is found individually in other proteins
What are DNA Binding motifs?
Independently folded proteins containing at least one structural motif that can recognise single/double stranded DNA
What is the function of beta barrels?
Acts as transporters for ions and small molecules
How do the domains present in haemoglobin show evolutionary characteristics from myoglobin?
Each chain if haemoglobin has a tertiary structure similar to the single chain of myoglobin
How do motifs bind to the major groove in DNA?
α helices or β sheets are inserted into the major grooves in a sequence specific manner
Where are motifs found?
Many different protein motifs exist in unrelated proteins that share functional properties
Name some examples of motifs in the body
- Calmodulin
- Greek Key Motif
- Beta Barrel
- Parallel Beta Sheets
Why do motifs bind to the DNA helix major groove?
The major groove contains sufficient information to distinguish one DNA sequence form any other
Describe the structural properties of a domain
- typically larger
- can be contiguous segments
- functional units
- modular in nature
Explain what the Helix turn Helix consists of
2 short helices perpendicular to one another, connected by a turn
What is the result of domain shuffling?
Causes modular units of function being conserved but shuffled between genes
What is the role of the EF hand motifs?
Allow the binding of Ca2+ for myosin light chain
Describe the structure of the Helix Loop Helix motif
Exists as a homo- and heterodimers
Central part made up of overlapping helices - form structure enabling dimerisation
Terminal ends of lower opposing helices contain basic amino acids - interact with DNA major groove
How can the leucine zippers regulatory function be increased?
Heterodimerisation expands the regulatory potential of leucine zippers
Where is the 7 transmembrane arrangement seen in polypeptides in the body?
Found in
- Rhodopsin
- Thyroid Stimulating Hormone Receptor (TSHR)
- Pharamalogical receptors
- Polypeptide hormone receptors
Describe the structure of the EF hand motifs
Helix loop helix motif
enables calmodulin and troponin binding
Where are helix turn helix motifs commonly found?
In prokaryotic and eukaryotic DNA binding proteins
Which part of the leucine zipper enables interactions with DNA major groove?
The lower helix dominated by basic amino acids forming a motif to interact with DNA major groove
What is Domain shuffling?
Segments of genes coding for functional domains are shuffled between different genes during evolution
Which motifs are present in calmodulin?
Contains 4 EF hand motifs each binding single calcium atoms
Explain what a heterodimer is
An oligomer made of 2 different monomers
What is the structure of the Zinc finger motif?
α helix and β sheet held together by non covalent interactions with Zinc
- dimer with two motifs on separate polypeptide chains
- each chain contains 2 Zn atoms
Name an example of a helix turn helix motif containing protein
Cro repressor protein
What is Calmodulin?
Calcium modulated protein
What is the Greek Key Motifs structure?
Consists of 4 anti parallel beta strands
connected by hydrogen bonds
How do Transcription Factors obtain their function?
Each TF contains a small no. of conserved motifs which combine to form functional domains allowing interactions with DNA
How is the coil in a Leucine Zipper motif held together?
By hydrophobic interactions down the opposing sides
Give an example of a common domain
The 7 transmembrane arrangement of α helices
What are transcription factors?
Proteins that bind to DNA regulating transcription
What is the function of the Zn atoms on the polypeptide chains in the zinc finger motif?
Provides stability to the recognition helix and loop structure
Where are structural & functional domains commonly found?
Individual domains can be found in different proteins (not necessarily with the same group of domains as in one protein)
Commonly represented in membrane bound receptors
What is a homodimer?
Oligomer formed from 2 identical monomers
How does the Cro protein operate?
Binds to DNA major groove
Recognition helix interacts with nucleotides
Represses transcription
Explain the common structure of functional and structural domains
Come in several forms; most commonly in bundles
- bundles of α helices or β sheets
- lone helices
What is the role of the conserved motifs in transcription factors?
They form DNA binding domains that allow regulatory function of their respective proteins
Which part of the zinc finger motif structure interacts with the DNA major groove?
α helix of each structure interacts with the major groove an recognises specific DNA sequences
What do the basic amino acids in the Helix loop Helix motif give rise to ?
Gives rise to the b/HLH functional domain
What is the function of the cro protein?
Recognises palindromic sequences
Represses Transcription
What are the different types of DNA binding motifs?
- Helix loop Helix
- Helix turn Helix
- Leucine Zipper
- Zinc Finger
Which proteins contain Zinc finger motifs?
Many hormone receptors e.g.
- Glucocorticoid
- Mineralocorticoid oestrogen
- Progesterone
- Vitamin D receptors
Describe the structure of a Leucine Zipper motif
Formed from 2 contiguous α helices
- dimetric protein formed from 2 polypeptides
- the dimers ‘zip’ together in top ‘stalk’ - forming short coiled coil
How do proteins incorporate all the folding into one structure?
Proteins fold into 3 basic units of structure which combine to provide complexity and diversity
How much of the motifs are conserved?
Motifs are conserved across all phyla
Give examples of protein structures containing helix loop helix motifs
- MAX gene
- MAD gene
- MYC gene
- MyoD regulatory factor