Modular Structure of Proteins Flashcards
What is a motif?
- A simple definition of a motif is a minimum arrangement of independently forming secondary structures combining recognisable folds (arrangements) across many different proteins.
(OR)
- A combination of two or more secondary structures to form a recognisable folded arrangement.
[It is not the tertiary structure. A motif can be recognised in a teritary structure or a quaternary structure.]
What are domains?
- Domain can be defined as a more complex structure at the tertiary or quaternary level, oftern involving interaction between distant parts of a protein or motif.
- Usually they are responsible for a particular function or interaction, contributing to the overall role of a protein.
What is the difference between motifs and domains?
- The difference between a motif and a domain is sometimes blurred, but domains more clearly define a functional unit than a motif.
- Both are evolutionarily conserved and are modular in nature.
List four examples of protein motifs.
- EF HAND: Ca2+ binding. E.g. Calmodulin and troponin- C resembles a helix but combines with a metal ion such as calcium.
- GREEK KEY MOTIF: These consist of antiparallel β strands, but it is a motif that is so common that it isn’t generally associated with a specific function.
- BETA BARREL: β strands wrapped around to form a circular tunnel.
- β-α-β MOTIF: parallel strands of a β sheet interlinked with an α helix to form the β-α-β motif.
How do DNA binding motifs work?
The helices can be inserted into the major groove of DNA in a sequence specific manner.
What are the four DNA binding motifs?
- Helix-loop-helix.
- Helix-turn-helix.
- Leucine zipper.
- Zinc finger.
Expand on transcription factors and motifs/domains.
- They are proteins that bind to DNA and regulate transcription.
- There are many different transcription factors but they each contain a small number of conserved motifs which combine to form domains that interact with the DNA.
- These motifs are conserved across all phyla (ie huge variety of eukaryotes, ranging from fungi to plants and animals).
- These motifs form DNA binding domains that allow the regulatory function of their respective proteins.
Why are α helices important in DNA binding?
- Alpha helices can fit within the major groove of DNA.
- The amino acid sequence of a DNA binding motif provides specificity.
- Different DNA binding domains & motifs present the binding helix using different arrangements of the structural motif.
Describe the helix-loop-helix motif.
- It only binds to DNA in the dimeric form.
- It can exist as hetero- (different monomers) or homodimers (same monomer).
- The central portion formed from overlapping helices form a structure that enables dimerisation.
- The terminal part of the lower opposing helices contain basic (positively charged) amino acids that interact with the major groove of the DNA (negatively charged) – giving rise to the b/HLH functional domain.
- Examples include mad, max, myc, myoD, etc.
Describe the helix-turn-helix motif.
- It consists of two short helices (one of which is the recognition helix) orientated at right angles to each other and connected by a “turn”.
- The motif is found in both prokaryotic and eukaryotic DNA binding proteins, for example, the CRO repressor and homeobox proteins.
- The CRO protein is a homodimer.
- CRO recognises palindromic sequence and, by binding to DNA, represses transcription.
- Only the recognition helix interacts with the nucleotide sequence itself and, like other DNA binding motifs, it locates within the major groove.
Homodimer meaning - A dimer made up of two identical subunits.
Palindromic sequence meaning - It is a sequence made up of nucleic acids within double helix of DNA and/or RNA that is the same when read from 5’ to 3’ on one strand and 5’ to 3’ on the other, complementary, strand.
Describe the leucine zipper motif.
- This motif is formed from 2 contiguous alpha helices and like the HLH (helix-loop-helix), is a dimeric protein formed from two polypeptide chains.
- The dimers “zip” together in the top “stalk” to form a short “coiled-coil”.
- The coil is held together by hydrophobic interactions down opposing sides of the helix.
- As in the b/HLH, basic amino acids dominate the lower part of the helix (forming a motif) and interact with the DNA major groove.
- Heterodimerisation expands the regulatory potential of leucine zippers.
Heterodimerisation meaning - A dimer, especially a biologically active one, derived from two or more different monomers.
Describe the zinc finger motif.
- This motif is an α-helix and a β-sheet held together by non-covalent interactions with zinc.
- The zinc atoms stabilise the recognition helix and the loop structure.
- The alpha helix of each motif interacts with the major groove of DNA and recognises a specific DNA sequence.
- Many proteins that possess the motif are hormone receptors, including Glucocorticoid, Mineralocorticoid, Oestrogen, Progesterone, Vit D receptors, etc.
