W5 Modular structure of proteins

Question 1

Alpha/beta contigous

Answer 1

alpha helix (single contiguous structure)

Beta sheets (are formed from non-contiguous beta strands connected by loops either in antiparallel or parallel arrangement

Question 2

Structural motifs

Answer 2

A motif is a minimum arrangement of independently forming secondary structures combining recognisable folds (arrangements) across many different proteins

A combination of two or more secondary structures to form a recognisable folded arrangement

(They are an independent order of structure)

Question 3

Sequence motif

Answer 3

A protein sequence motif is a pattern of amino acids that are found in related genes or proteins

Question 4

Domain

Answer 4

A more complex structure at the tertiary or quaternary level, often involving interaction between distant parts of a protein or motifs (may be at opp. ends of pp chian thus bringing ends to close proximity)

A functional domain is typically larger and may or may not be a contiguous segments of the polyptide chain

Question 5

Greek key motif

Answer 5

Consists of antiparallel beta strands but is one motif that is so common it isn’t generally associated with a specific function

Question 6

DNA binding motifs

Answer 6

Helices can be inserted into the major groove of DNA in a sequence specific manner

Helix loop helix – eg Max & Mad also Ca2+ binding (not exclusive)

Helix turn helix –eg Cro, tryptophan, & lac repressors

Leucine Zipper – eg GCN4 (translation in yeast)

Zinc Finger – eg hormone receptors (transcription regulation)

Question 7

Functional domain - membrane bound receptors

Answer 7

Bundle of alpha helices or less commonly lone helices or bundle of beta sheets

Bundle of alpha-helices each one of @20 aa spans membrane

Hydrophobic
Side chains locate the bundle in the membrane

The 7-transmembrane arrangement of alpha helices is common.
Found in rhodopsin, TSHr, many pharmacological receptors and also receptors for some polypeptide hormones

Question 8

Domain shuffling

Answer 8

In the genome results in modular units of function being conserved but shuffled between genes

Question 9

The Globin domain - Comparison of haemoglobin and myoglobin

Answer 9

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

Question 10

Transcription factors domain

Answer 10

Each contain a small number of conserved motifs - combine to form domains that interact with the DNA

Conserved across all phyla

Form DNA binding domains that allow the regulatory function of their respective proteins

Interact w/DNA only in dimeric form

Question 11

Alpha helices are important in DNA binding

Answer 11

Can fit w/in the major groove (on recognition helix)

AA sequence of a DNA binding motif = specificity

Different DNA binding domains & motifs present the binding helix using different arrangements of the structural motif

Question 12

Helix-loop-helix motif

Answer 12

Binds DNA only in the dimeric form

Exists as heterodimers + homodimers

Central portion = overlapping helices that form a structure enabling dimerization

Terminal part of the lower opposing helices contain basic amino acids that interact with the major groove of the DNA – giving rise to the b/HLH functional domain

Question 13

Heterodimers

Answer 13

Allows use of TF beyond dingle sequence motif w/in DNA as allows to interact w/sequences that are not palindromic

Question 14

Leucine zipper motif

Answer 14

Formed from 2 contiguous alpha helices = dimeric protein

Dimers “zip” together in the top “stalk” to form a short “coiled-coil”

Coil 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 (AA stabilise overall interaction w/DNA)

Heterodimerisation expands the regulatory potential of leucine zippers

Question 15

Helix-turn-helix motif

Answer 15

Two short helices orientated at right angles to each other & connected by a “turn”

Found in both prokaryotic and eukarotic DNA binding proteins eg CRO repressor, & homeobox proteins

Question 16

CRO protein

Answer 16

Homodimer (recognises same sequence on both sides)

Recognises palindromic sequence and by binding DNA represses transcription

Only recognition helix interacts w/nucleotide sequence itself + like other DNA binding motifs it locates w/in the major groove

Helix-turn-helix motif

Question 17

Zinc finger motif

Answer 17

An alpha helix and a beta sheet held together by non-covalent interactions w/zinc

Dimer w/ 2 motifs on separate PP chains each containing two zinc atoms stabilising the recognition helix and loop structure

Alpha helix of each motif interacts w/major groove of DNA and recognises a specific DNA sequence

Among the proteins that have zinc fingers include many of the hormone receptors