南京大学-杨荣武生物化学-英文版-第一篇-ProteinIII

Molecules with similar shapes can interact in similar ways.
☺For example, morphine, heroin, and other opiate drugs are similar enough in shape that they can bind to the same receptors as natural signal molecules, called endorphins. ☺Binding to the receptors produces euphoria and relieves pain.
☻ hmm… seems like different organisms share similar biochemical processes ☻ well, seems like proteins in charge of the similar biochemical processes in different organisms are similar in many ways e.g. size, pI … etc ☻ e.g. cytochrome C in respiration
mouse
yeast
plant
And many other different organisms…
They believed that different organisms carried out very different biochemical reactions
But slowly and slowly they realized…
Beta Keratin
Proteins that form extensive beta sheets Found in silk fibers Alternating sequence: Gly-Ala/Ser-Gly-Ala/Ser.... Since residues of a beta sheet extend alternately above and below the plane of the sheet, this places all glycines on one side and all alanines and serines on other side! This allows Glys on one sheet to mesh with Glys on an adjacent sheet (same for Ala/Sers)
– – – – 4-hydroxyproline 3-hydroxyproline 5-hydroxylysine Proe 30% of res.
The Collagen Triple Helix
A case of structure following composition The unusual amino acid composition of collagen is unsuited for alpha helices OR beta sheets But it is ideally suited for the collagen triple helix: three intertwined helical strands Much more extended than alpha helix, with a rise per residue of 2.9 Angstroms 3.3 residues per turn Long stretches of Gly-Pro-Pro/HyP
Structural basis of the collagen triple helix
Every third residue faces the crowded center of the helix - only Gly fits here Pro and HyP suit the constraints of phi and psi Interchain H-bonds involving HyP stabilize helix Fibrils are further strengthened by intrachain lysine-lysine and interchain hydroxypyridinium crosslinks
Polypeptide Chains
Triple-helix conformation
– Gly must occupy every third residue
• No side chains • Small enough to fit inside the helix
– Gly aligned with X residue of one chain and Y residue of third chain
Homologous proteins
Similar sequence Similar structure Similar function Evolved from common ancestor Belong to protein family
Fibrous Proteins
Much or most of the polypeptide chain is organized approximately parallel to a single axis Fibrous proteins are often mechanically strong Fibrous proteins are usually insoluble Usually play a structural role in nature
Comparison of cytochrome c sequences
Cytochrome c:
similar sequences- similar structures-same function
fish
bacteria
bacteria
50 amino acid difference Sequence is known in over 80 species
Phylogeny of Cytochrome c
The number of amino acid differences between two cytochrome c sequences is proportional to the phylogenetic difference between the species from which they are derived This observation can be used to build phylogenetic trees of proteins This is the basis for studies of molecular evolution
• Staggered arrangement in helix by one residue
– Mutation that causes replacement of Gly leads to defective molecules and disease
• Osteogenesis Imperfecta
Alpha Keratin
Found in hair, fingernails, claws, horns and beaks Sequence consists of 311-314 residue alpha helical rod segments capped with non-helical N- and Ctermini Primary structure of helical rods consists of 7-residue repeats: (a-b-c-d-e-f-g)n, where a and d are nonpolar. Promotes association of helices!
Collagen - A Triple Helix
Principal component of connective tissue (tendons, cartilage, bones, teeth) basic unit is tropocollagen:
– three intertwined polypeptide chains (1000 residues each – MW = 285,000 – 300 nm long, 1.4 nm diameter – unique amino acid composition
What can be learned from amino acid sequence of cytochrome c?
1. Found in all species that use oxygen: bacteria-humans 2. Most have 104 amino acids, 26/104 invariant 3. Evolved >1.5 billion years ago, before divergence of plants and animals 4. # amino acids differences between 2 species proportional to time of evolutionary divergence 5. Amino acid differences are not random 6. Amino acid differences survived natural selection
Collagen Structures
Triple Helix
Collagen fibers are stabilized and strengthened by Lys-lys cross-links.