CHMI 2227E Biochemistry I Proteins: Secondary Structure Beta Strands and Beta Sheets Loops and Turns A special case: Collagen CHMI 2227 - E.R. Gauthier, Ph.D.

Beta Strands and Beta Sheets The other common secondary structure is called the β structure which includes β strands and β sheets β strands are portions of the polypeptide chain that are almost fully extended having a “zig-zag” shape β strands are flexible but not elastic CHMI 2227 - E.R. Gauthier, Ph.D.

Beta Sheets When multiple β strands are arranged side-by-side, they form β sheets; Proteins rarely contain isolated β strands because the structure by itself is not significantly more stable than other conformations However, β sheets are stabilized by hydrogen bonds between carbonyl oxygens and amide hydrogens on adjacent β strands. CHMI 2227 - E.R. Gauthier, Ph.D.

Hydrogen Bonded Beta Strands The H-bonded β strands can be on separate polypeptide chains or on different segments of the same chain The β strands in a sheet can be either parallel (running in the same N- to C- terminal direction) or antiparallel (running in opposite N- to C- terminal direction) N C N C N C C N CHMI 2227 - E.R. Gauthier, Ph.D.

Antiparallel Beta Strands The hydrogen bonds are nearly perpendicular to the extended polypeptide chains The carbonyl oxygen and the amide hydrogen atoms of one residue form hydrogen bonds with the amide hydrogen and carbonyl oxygen of a single residue in the other strand http://dbs.umt.edu/courses/fall2006/bioc380/lectures/011/lecture.html CHMI 2227 - E.R. Gauthier, Ph.D.

Parallel Beta Strands In the parallel arrangement, the hydrogen bonds are not perpendicular to the extended chains, and each residue forms hydrogen bonds with the carbonyl and amide groups of two different residues on the adjacent strand http://dbs.umt.edu/courses/fall2006/bioc380/lectures/011/lecture.html CHMI 2227 - E.R. Gauthier, Ph.D.

Mixed Beta Sheets Many strands, typically 4 or 5 but as many as 10 or more, can come together in β sheets. Such sheets can be purely antiparallel, purely parallel, or mixed CHMI 2227 - E.R. Gauthier, Ph.D.

Beta Sheet Conformation The R groups from the amino acids point alternatively above and below the plane of the sheet http://dbs.umt.edu/courses/fall2006/bioc380/lectures/011/lecture.html CHMI 2227 - E.R. Gauthier, Ph.D.

Beta Pleated Sheets Beta Pleated Sheets: Silk In certain proteins adopting a β conformation, small R groups from amino acids such as Ala, Gly and Ser allow the β sheets to stack closely together; This β conformation is responsible for the flexible characteristic of the silk filaments Example: Silk Fibroin CHMI 2227 - E.R. Gauthier, Ph.D.

Loops and Turns In an α-helix or a β strand, consecutive residues have a similar conformation that is repeated throughout the structure; Most of these regions of secondary structures can be characterized as loops and turns since they cause directional changes in the polypeptide backbone; CHMI 2227 - E.R. Gauthier, Ph.D.

Loops and Turns Loops and turns connect α-helices and β strands and allow the polypeptide chain to fold back on itself, producing the compact 3D shape seen in native structures; Loops often contain hydrophilic residues and are usually found on the surfaces of proteins where they are exposed to solvent and form H-bonds with water CHMI 2227 - E.R. Gauthier, Ph.D.

Loops and Turns Loops containing only a few (up to 5) residues are referred to as turns if they cause an abrupt change in the direction of a polypeptide change; The most common types of tight turns are called reverse turns or β turns because they usually connect different antiparallel β strands CHMI 2227 - E.R. Gauthier, Ph.D.

Beta turns β turns contain 4 amino acid residues and are stabilized by hydrogen bonding between the carbonyl oxygen of the first residue and the amide hydrogen of the fourth residue; β turns produce an abrupt (usually about 180°) change in the direction of the polypeptide chain Gly and Pro are often part of the β turns Pro is capable of forming a cis peptide bond conformation which is highly susceptible in forming β turns Glycine has a small R group which is capable of generating unique psi and phi angles permitting a high degree of flexibility http://web.chemistry.gatech.edu/~williams/bCourse_Information/6521/protein/secondary_structure/beta_turn/down/beta_turn_1.jpg CHMI 2227 - E.R. Gauthier, Ph.D.

A special case : collagen Family of over 20 rod-like proteins; Important part of connective tissue (1/3 of all proteins in mammals); Classified into 5 different types, according their amino acid content, their primary structure and their sugar content. Type I bone, tendon, fibrocartilage, dermis, cornea Type II nucleus pulposus, hyaline cartilage Type III intestinal and uterine wall Type IV endothelial, epithelial membranes Type V* cornea, placenta, bone, heart valve * Found in small quantities CHMI 2227 - E.R. Gauthier, Ph.D.

A special case : collagen Chain 1 Chain 2 Chain 3 Consists in a triple helix: 3 polypeptide chains (each left handed) are intertwined together to form a right-handed superhelix; For each left-handed helix: Pitch: 0.94 nm Rise: 0.31 nm per residue 3 residues per turn 1000 residues per chain So: the collagen helix is more extended than the a-helix (from Kadler, 1996) Triple helix CHMI 2227 - E.R. Gauthier, Ph.D.

A special case : collagen Type V collagen = 1839 a.a.!! CHMI 2227 - E.R. Gauthier, Ph.D.

A special case : collagen Hypro 5-Hylys The collagen polypeptides have a very specific amino acid composition: 1/3 Gly 1/4 Pro 1/4 Hypro (hydroxyproline) and 5-Hylys (hydroxylysine) These residues follow a strict sequence where Gly is always repeated every third position – WHY??; CHMI 2227 - E.R. Gauthier, Ph.D.

A special case : collagen 13 CHMI 2227 - E.R. Gauthier, Ph.D.

A special case : collagen The presence of Gly at every third residue allows each collagen chains to form a tightly wound helix that can accommodate Pro/Hypro (which are otherwise rarely included in helices); Since the helix has 3 a.a. per turn, having Gly at every third residue means that Gly is always on the same side of the helix; It just so happens that Gly is always positioned at the center of the triple helix; This allows close packing of the three helices, which can interact and yield a very strong, rope-like structure. CHMI 2227 - E.R. Gauthier, Ph.D.

Hydrogen bonds stabilize the collagen triple helix Gly of Chain 1 Pro of Chain 2 G Glycine Hypro Pro CHMI 2227 - E.R. Gauthier, Ph.D.

Formation of collagen fibers Collagen triple helix (tropocollagen) Lysine CHMI 2227 - E.R. Gauthier, Ph.D.

Formation of collagen fibers Transmission electron microscopy of collagen fibers CHMI 2227 - E.R. Gauthier, Ph.D.

Collagen, Vitamin C and scurvy The formation of Hypro requires the enzymatic modification of Pro in a reaction which involves: Prolyl hydroxylase (an enzyme) Fe+2 Ascorbic acid, a derivative of Vit C and an antioxidant, keeps iron in its reduced Fe+2 form, and not the oxidized, more stable Fe+3 form. Humans cannot make Vit C on their own; In the absence of Vit C, the collagen triple helix cannot assemble properly, leading to a much softer connective tissue. CHMI 2227 - E.R. Gauthier, Ph.D.