Protein Fold Classes

1
Protein Fold Classes Structural Motifs

• Dr. Abdelkrim Rachedi,
• Wits Bioinformatics,
• Wits University

2
Protein Structural Motifs

• The term Motif refers to a well defined
  structural pattern that reoccur in protein
  structure.
• Helices
• Beta Strands Sheets
• Turns Loops

3
The Right Handed Helix - Alpha-Helix
4
The Right Handed Helix - 310 Helix
5
The Right Handed Helix - Pi Helix
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Helix Bundle

• 4-helix bundle Human growth hormone, a signaling
  molecule.

7
The Beta Stand
8
The Beta Stands Sheets - Parallel Beta
Sheet
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The Beta Stands Sheets - Anti-Parallel
Beta Sheet
10
Beta HairPin
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Beta Barrels Fold Types

• - Up-and-down beta barrel
• It's the simplest barrel topology and consist of
  a series of beta strands adopting mostly
  anti-parallel formation.
• - Greek key
• Beta strands adjacent in space that are not
  adjacent in sequence. Beta barrels generally
  consist of at least one Greek key structural
  motif linked to a beta hairpin, or two successive
  Greek keys.
• - Jelly roll
• Also known as the Swiss roll, is a complex
  nonlocal structure in which a number of pairs
  (four) of anti-parallel beta sheets, only one of
  which is adjacent in sequence, come together in
  3D-space forming barrel shape.

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Up-and-Down beta-barrel

• - Eight-strand barrel -
• The human retinol-binding protein (RBP)

13
Beta Barrel

• Eight-strand barrel binding retinol (vitamin A).

14
Greek Key

• Greek key refers to a kind of protein structural
  motif. It is named for its resemblance to the
  Greek key pattern in art.

15
Jelly Roll

• A PDB entry, 1xe7, showing a Jelly Roll
  beta-barrel

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Turns and Loops
17
Turns Definition

• - Turns can be defined by the close approach of
  two Ca atoms (lt 7 Å) in a stretch of residues not
  folded into a common secondary structure.
• note the Beta Hairpin is a special type of a
  beta Turn. (see above)

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Turns types (some)

• - a-turn a hydrogen bond(s) formed between
  residues are separated by four residues (i ? i
  4).
• - ß-turn (the most common form) a hydrogen
  bond(s) between residues separated by three
  residues (i ? i 3).
• - ?-turn a hydrogen bond(s) between
  residues separated by two residues (i ? i 2).
• - p-turn a hydrogen bond(s) between
  residues separated by five residues (i ? i 5).

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Beta Bulge (Note the image below
is just a construction)
20
Protein Structural Fold Classes (in PDB)

• - Fold refers to a global type of structural
  arrangement.
• -The number of unique folds that proteins adopt
  is limited.
• - Almost all protein structures in the PDB can be
  classified into one of more of the fold
  categories Alpha, Beta and Alpha-Beta folds.
• - The fold categories are annotated in databases
  such as CATH and SCOP (for URL links see Tools
  slide).

21
Protein Structural Classes (in PDB) 1-
Alpha Proteins

• - Proteins mostly made of a-helices.
• e.g. Haemoglobin (PDB 1zgx)
• - e.g. check SCOP at http//scop.mrc-lmb.cam.ac.uk
  /scop/data/scop.b.b.html
• - check also CATH (url below)

22
Protein Structural Classes (in PDB) 2-
Beta Proteins

• - Proteins mostly made of ß-sheets.
• e.g. (PDB 1a08, ß-barrel protein)
• - e.g. check SCOP at http//scop.mrc-lmb.cam.ac.uk
  /scop/data/scop.b.c.html
• - check also CATH (url below)

23
Protein Structural Classes (in PDB) 3-
Alpha-Beta Proteins

• - Proteins made of a-helices and ß-sheets.
• This fold in the most populous category.
• e.g. DHFR (PDB 3dfr)
• - e.g. check SCOP at http//scop.mrc-lmb.cam.ac.uk
  /scop/data/scop.b.d.html
• and http//scop.mrc-lmb.cam.ac.uk/scop/data/scop
  .b.e.html
• - check also CATH (url below)

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Why study folds and motifs

• - Perhaps the corner stone of Structural
  Bioinformatics is to be able to predict structure
  function of proteins from their amino acids
  sequence.
• - similar functions may be associated with
  certain folds of proteins, and the fold
  classification therefore, serves as an important
  tool in understanding the possible function of a
  protein.
• - Statistical analysis of folds and motifs would
  help create robust prediction algorithms.

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Tools

• - CATH http//www.cathdb.info/
• - SCOP http//scop.mrc-lmb.cam.ac.uk/scop/
• - Standard motifs builder (including DNA)
  http//www.bioinformer.co.uk/bscmpd/html/bsps/

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References

• Richardson JS. (1981). "The anatomy and
  taxonomy of protein structure". Adv Protein Chem
  34 167-339
• Pavone V, Gaeta G, Lombardi A, Nastri F, Maglio
  O, Isernia C, Saviano M. (1996). "Discovering
  protein secondary structures classification and
  description of isolated alpha-turns". Biopolymers
  38 (6) 705-21
• Venkatachalam CM. (1968). "Stereochemical
  criteria for polypeptides and proteins. V.
  Conformation of a system of three linked peptide
  units". Biopolymers 6 (10) 1425-36
• Milner-White EJ and Poet R. (1987). "Loops,
  bulges, turns and hairpins in proteins". Trends
  Biochem Sci 12 189-192.
• Richardson JS, Getzoff ED, Richardson DC.
  (1978). "The ß-bulge a common small unit of
  nonrepetitive protein structure". Proc Natl Acad
  Sci U S A 75 (6) 2574-8.
• Richardson J. S. (1981). "The anatomy and
  taxonomy of protein structure". Adv Protein Chem
  34 167-339.
• Chan AW, Hutchinson EG, Harris D, Thornton JM.
  (1993). "Identification, classification, and
  analysis of beta-bulges in proteins". Protein Sci
  2 (10) 1574-90.