Supersecondary Structures (structural motifs)

Transcription

1 Supersecondary Structures (structural motifs) Various Sources Slide 1

2 Supersecondary Structures (Motifs) Supersecondary Structures (Motifs): : Combinations of secondary structures in specific geometric arrangements Simple supersecondary structures consisting of 3 or fewer secondary structures considered here Simple supersecondary structures consisting of 3 or fewer secondary Large supersecondary structures (ie. Greek Key and Jelly-Roll) consisting of more than 3 secondary structures will be considered along with tertiary structures and folds Why? Large supersecondary structures can be domains. Large supersecondary structures (ie. Greek Key and Jelly-Roll) consisting of Simple supersecondary structures are typically composed of two secondary structures (ie. strands or helices) and a turn (or loop) Helix-turn-helix DNA binding motif Slide 2

3 Supersecondary Structures (Motifs) Supersecondary Structures (Motifs): : Combinations of secondary structures in specific geometric arrangements Hierarchy of Protein Structure α β Simple supersecondary structures are the 'building blocks' of. αα βαβ ββ a) Complex Supersecondary Structures b) Tertiary Structure / Domain folds Simple supersecondary structures are relatively stable components of the 'Molten Globule' protein folding intermediate αααα 4 helix bundle βαβαβ Rossman fold βββ β-meander ββββ Greek Key Slide 3

4 β-hairpin Simple and Common supersecondary structure β-hairpin: : two antiparallel β-strands joined by a turn or loop Very small supersecondary structure (typically less than 10 residues) β-hairpin Turn: : Short loop segment joining two antiparallel β-strands Hairpin turns are a special case of Reverse turns Favor type I' and II' turns in contrast to reverse turns which favor type I and II β-hairpin supersecondary structures are further subdivided based upon the size of the β-hairpin turn. Slide 4

5 2 Residue β-hairpins β-hairpin turns (2 residues) are almost always a Type I' or Type II' (right) Type I' X-Gly Residue 1 (left-handed helix) favors Gly, Asp or Asn (High turn propensity) Residue 2 is almost always Gly (disallowed region of Ramachandran for non-gly) Type II' Gly-X Residue 1 is almost always Gly Residue 2 favors small polar (Ser, Thr) Bioinformatics Presence of Gly between predicted β-strands (ie. suggests a possible β-hairpin turn) increases 'confidence' of prediction Slide 5

6 3 Residue β-hairpins Residues at ends of β-sheets often make only a single H-bonds (typically has two H-bonds) Intervening 3 residues have distinct conformational preferences Residue 1 Residue 2 Residue 3 right-handed helical conformation bridge region between helix and sheet left-handed helical conformation (favors Gly, Asn, Asp) Bioinformatics Presence of Gly, Asn or Asp between predicted β-strands (ie. suggests a possible β-hairpin turn) increases 'confidence' of prediction Slide 6

7 4 Residue β-hairpins Last common β-hairpin Intervening 4 residues have preferred conformations Residue 1 Residue 2 Residue 3 Residue 4 right-handed helical conformation right-handed helical conformation bridge region between helix and sheet left-handed helical conformation (favors Gly, Asn, Asp) Bioinformatics Presence of Gly, Asn or Asp between predicted β-strands (ie. suggests a possible β-hairpin turn) increases 'confidence' of prediction Slide 7

8 Long Loop β-hairpins Ω loop Wide-range of conformations with no particular sequence preferences Long loop β-hairpins are special case of Ω loops Often referred to as a 'random coil' conformation Loop looks similar to the Greek Letter Ω Consecutive antiparallel β-strands joined by long loop β-hairpin turns are referred to as the β-meander supersecondary structure Consecutive antiparallel Slide 8

9 β-corner (revisted) β-corner two residue disruption of β-sheet hydrogen bonding β-corners can also be thought of as a supersecondary structure consisting of a β-hairpin with a two residue β-bulge 90 change in direction of β-strand Gly typically opposite the β-bulge Antiparallel sheet with β-corner Slide 9

10 Helix (or αα) hairpins αα-hairpin two antiparallel α-helices connected by a loop Long loops have many possible conformations (and sequences) Shortest loops (2 and 3 residues) have only a single allowed conformation αα-hairpin Parallel and antiparallel helices generally interact via hydrophobic interactions Requires one hydrophobic residue per turn of helix of each helix αα-hairpins typically involve amphipathic helices Slide 10

11 Helix (or αα) hairpins 2 residue αα-hairpin (right) X-Gly Loop is ~ perpendicular to helix axes Residue 1 has a bridging conformation (between α and β) Residue 2 must by Gly 3 residue αα-hairpin (not shown) X-Gly Residue 1 has a bridging conformation (between α and β) Residue 2 has left-handed helical conformation Residue 3 has a β-strand conformation Residue 1 of the αα-hairpin turn caps the first helix Residue 2 of the 2 residue αα-hairpin turn caps the terminii of both helices Slide 11

12 4 residue Helix (or αα) hairpins αα-hairpin two antiparallel α-helices connected by a loop Only two possible conformations for 4 residue αα-hairpin turns Conformation 1) Similar to 3 residue αα-hairpin turn (4 residue is in β-strand conformer Residue 1 Bridging Residue 2 left-handed helix Residues 3 & 4 β-strand Conformation 2) Residues 1 & 3 Residues 2 & 4 β-strand Bridging αα-hairpin Slide 12

13 Helix (or αα) corners αα-corner two roughly perpendicular α-helices connected by a short loop Shortest loop is 3 residues long and adopts a single allowed conformation Residue 1 Small (Gly or Ala) to avoid steric conflicts Residue 2 Hydrophobic residue inserted between α-helices Residue 3 Small polar residue (Ser or Asp) Residue 1 & 3 cap the first and second helices, respectively N Virtually all αα-corners are right-handed due to steric conflicts in left-handed corners C αα-corner (right handed) Left Handed Right Handed Slide 13

14 Functional Motifs eg. Helix-turn-Helix (a.k.a. EF-Hand) Loop regions connecting helices - can have important biological functions - resulting supersecondary structures are both structural and functional Functional supersecondary structure (ubiquitous) involved in Ca 2+ binding Note: EF-Hands always occur in pairs that pack against one another 12 residue loop between helices Invariant Gly at position 6 Asp and Glu required at 4 positions (direct Ca2+ interaction) Troponin C Slide 14

15 Helix 1 Functional Motifs eg. Helix-loop-Helix Loop regions connecting helices - can have important biological functions - resulting supersecondary structures are both structural and functional Functional supersecondary structure (procaryotes primarily) involved in DNA binding Helix 2 lies within major groove of B-DNA Helix 1 and loop position Helix 2 within major groove Sequence differences in Helix 2 give rise to specificity for different DNA sequence Helix 2 Cro repressor (phage λ) Note: Helix-turn-Helix supersecondary structures always occur in pairs as they recognize palindromic sequences Slide 15

16 βαβ-motif Parallel β-sheets are connected by longer segments of polypeptide chain (in comparison with antiparallel) Frequently (most examples), the connections between parallel β-sheets contain helices forming the βαβ structural motif Helix is parallel to the β-sheet and the connections are variable in length Virtually all βαβ have a right-handed twist Viewed along the sheet edge Clockwise rotation from front to back Slide 16