Lecture 28 - Modular structure of Proteins Flashcards Preview

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Flashcards in Lecture 28 - Modular structure of Proteins Deck (13):
1

Motifs and Domain overview (5)

Both are evolutionarily conserved and are modular in nature.
• Simple secondary structures (folds) combine to form structural motifs or larger functional domains.
• Different from sequence motifs (pattern of amino acids that are found in related genes or proteins).
• Motifs and Domains are an independent order of structure.
• They are an independent order of structure different from primary, secondary, tertiary and quaternary.

2

Motifs (3)

An element of structure or pattern that recurs in many contexts.
A minimum arrangement of secondary structure combining folds & is a small structural unit that can be recognised in a variety of proteins.
Motifs are organised or combined into larger structural and functional domains.

3

Domains (2)

A more complex structure that has a tertiary or quaternary structure of its own.
A functional domain is typically larger and may or may not be contiguous (being in actual contact: touching along a boundary) segments of the polypeptide chain.

4

Motif - examples (4)

• EF hand (4 hands to one calcium) - Ca2+ binding e.g. Calmodulin & Troponin-C resembles a helix turn helix but combines with a metal ion such as calcium. At either end EF hand present (two motifs).
• Greek Key motif consists of antiparallel beta strands but is one motif. It is very common, and it doesn’t have a specific function.
• Beta barrel – beta strands wrapped around to form circular tunnel.
• Parallel strands of a beta sheet interlinked with an alpha helix to form a beta-alpha-beta motif (named after structure).

5

Structural and functional domains (5)

One functional domain is a membrane bound receptors.
Come in several forms most commonly as bundles: Bundle of alpha helices or less commonly lone helices or bundle of beta sheets.
The 7-transmembrane arrangement of alpha helices is common e.g. rhodopsin, TSHr, many pharmacological receptors and receptors for some polypeptide hormones.

Individual domains can be found in different proteins.
Domain shuffling in the genome results in modular units of function being conserved but shuffled between genes.

6

The Globin domain (2)

Comparison of haemoglobin and myoglobin.
Each chain of haemoglobin has a tertiary structure very similar to that of the single myoglobin chain, strongly suggesting evolution from a common ancestral O2-binding polypeptide.

7

Motifs as one element in a domain (3)

Proteins involved in transcription contain 4 main different motifs.
They are not exclusive to DNA binding/ transcription factors.
DNA binding motifs – helices can be inserted into the major groove of DNA in a sequence specific manner.
o Helix loop helix – e.g. Max & Mad also Ca2+ binding
o Helix turn helix –e.g. Cro, tryptophan, & lac repressors
o Leucine Zipper – e.g. GCN4 (translation in yeast), cFos & cJun
o Zinc Finger – e.g. hormone receptors (transcriptional regulation as a result of hormone regulation).

8

Transcription Factors - Overview (4)

• Proteins that bind to DNA and regulate transcription.
• Many different transcription factors, each contain a small number of conserved motifs which combine to form domains that interact with the DNA.
• Motifs are conserved across all phyla (i.e. huge variety of eukaryotes, ranging from fungi to plants and animals).
• Motifs form DNA binding domains that allow the regulatory function of their respective proteins.

9

Transcription Factors - Helix loop helix (5)

 Binds DNA only in the dimeric form.
 Exists as hetero (different monomers) and homodimers (identical monomers).
 Central portion is made from overlapping helices that form a structure enabling dimerization.
 The terminal part of the lower opposing helices contains basic amino acids that interact with the major groove of the DNA – giving rise to the b/HLH functional domain.
 Examples include mad, max (also Ca2+ binding), myc, myoD.

10

Transcription Factors - Helix turn helix (6)

 Consists of two short helices orientated at right angles to each other & connected by a “turn”
 The motif is found in both prokaryotic and eukaryotic DNA binding proteins e.g. CRO repressor, & homeobox proteins.
 The CRO protein is a homodimer.
 CRO recognises palindromic sequence and by binding 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.
e.g. Cro, tryptophan, & lac repressors

11

Transcription Factors - Leucine Zipper (6)

 Formed from 2 contiguous alpha helices and like the HLH, 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 the example right is cFos partnered with cJun.
 e.g. GCN4 (translation in yeast), cFos & cJun.

12

Transcription Factors - Zinc Finger (6)

 An alpha helix and a beta sheet held together by non-covalent interactions with zinc.
 The diagram shows a dimer with 2 motifs on separate polypeptide chains each containing two zinc atoms stabilising the recognition helix and loop structure.
 The alpha helix of each motif interacts with the major groove of DNA and recognises a specific DNA sequence.
 Of note among the proteins that have zinc fingers include many of the hormone receptors such as:
 Glucocorticoid, Mineralocorticoid oestrogen, progesterone, Vit D receptors.
 e.g. hormone receptors (transcriptional regulation as a result of hormone regulation)

13

Alpha helices (3)

• Important in DNA binding as it 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.