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Unformatted text preview: Lecture 4
Chapter 2: Stryer
Proteins: • tertiary structure • quaternary structure • structure: ﬁbrous proteins (keratin, collagen, silk ﬁbroin) • protein classiﬁcation • protein folding
g ly c in e ( a m in o a c id ) life cycle of a protein 1) translation - synthesized on the ribosome based on genetic information (DNA and mRNA) - CHM 6640 2) function - catalysis, signaling, etc. (later chapters) protein needs to be 'folded' 3) degradation c h y m o tr y p s in ( p r o te in ) !-helical coiled coil Length: ~1000 Å (100 nm or 0.1 !m) association between nonpolar side chains Structure: two right-handed !-helices cross-linked by weak interactions such as van der Waals forces and ionic interactions; heptad repeat of amino acids; left-handed supercoil Function: ﬁbrous proteins provide structural support for cells and tissues !-keratin Heptad repeat: Every 7th residue is a leucine Crosslinks - covalent bonds between residue side chains exist within !-keratin to add strength and stability - these can be altered through ox/red reactions, as with a hair 'perm' !-keratin • major proteins of mammalian hair, nails, wool, claws, horns, hooves, quills, beaks, outer skin • sequence consists of ~300 residue right-handed, !-helical rod segments capped with nonhelical N- and C-termini • 1° structure of helical rods consists of 7-residue repeats (ab-c-d-e-f-g)n, where a and d are nonpolar - promotes formation of helical coiled-coil Collagen triple helix collagen Found in connective tissue (tendon, cartilage); helical, but not an ! helix; left-handed; 3-residues per turn; repeating tripeptide Gly-X-Pro or Gly-X-HyPro; three helical strands 'super helix' collagen collagen consists of higher-order (quaternary) structures, in which the twisted coiled-coil units assemble into ﬁlaments and ﬁbrils silk ﬁbroin ﬁbroin is a protein produced by spiders and insects ﬂexible & strong - tensile strength of 200,000 psi structure is largely antiparallel " sheet Tertiary (3°) structure Tertiary (3°) structure involves longer-range interactions between side chains or backbone. Stabilizing forces: H bonding, ionic interactions or 'salt bridges', van der Waals or hydrophobic interactions, disulﬁde linkages 'subunit' Quaternary (4°) structure Quaternary (4°) structure involves interactions between subunits, or individual polypeptide chains. Stabilizing forces: H bonding, ionic interactions or 'salt bridges', van der Waals or hydrophobic interactions size & shape of polypeptides (proteins) A comparison of how human serum albumin (molecular weight = 64,500 daltons or 64.5 kDa) would appear if it adopted each of the following forms: The helical & extended nature of the ﬁbrous proteins provide strength & stability; other proteins with different functions are often better served by having globular-like structures. Proteins can be loosely classiﬁed by shape and solubility
• ﬁbrous proteins -simple & regular linear structures -axial ratio (ratio of length to breadth) >10 -serve mainly structural roles -low solubility in water or dilute salt solutions • globular proteins -compactly folded, approximately spherical in shape -axial ratio <10 (but usually not >3-4) -serve many functional roles (e.g., enzymes) -generally water soluble (why?) • membrane proteins -found in membranes; frequently polyhelical structures -insoluble in water; require detergents side chain ionization If the solution pH < pKa of the functional group, the group is protonated If the solution pH > pKa of the functional group, the group is unprotonated tertiary (3°) structure – example of a globular protein: myoglobin tertiary (3°) structure – example of a globular protein: myoglobin heme group – present in myoglobin, hemoglobin, cytochromes, etc. ribbon mesh surface contour ribbon with side chains space ﬁlling porin: “inside out” amino acid distribution; what is it’s functional role? myoglobin: distribution of amino acids yellow: hydrophobic blue: charged compare interior and exterior other examples of globular proteins note side chains of the active site amino acids note disulﬁde bonds Protein folding patterns: Folds, motifs, supersecondary structures ! helix " sheet Protein folding: recurring patterns Folds, motifs, supersecondary structures ! " Protein folding: recurring patterns Folds, motifs, supersecondary structures quaternary (4°) structure – hemoglobin Complex 4° structure: coat of human rhinovirus !2"2
different meaning from ! in !-helix http://www.biochem.usyd.edu.au/LIVEMOLS/java/JavaMage/Hb.html How do each of these reagents cause protein denaturation? amino acid sequence of ribonuclease: note disulﬁde bonds How do proteins refold into the correct conformations? protein folding is highly cooperative Alternative conformations of a peptide sequence The protein model for priondisease transmission VDLLKN What are the effects on function? S t a n le y B . P r u s in e r T h e N o b e l P r iz e in P h y s io lo g y o r M e d ic in e 1 9 9 7 " fo r h i s d i s c o v e r y o f P r i o n s - a n e w b i o l o g i c a l p r i n c i p l e o f i n fe c ti o n " Protein classiﬁcation: !-protein Prions are infectious agents that do not have a nucleic acid genome. The protein alone is the infectious agent. Prions have been defined as "small proteinaceous in f e c t io u s p a r t ic le s w h ic h r e s is t in a c t iv a t io n b y p r o c e d u r e s t h a t m o d if y n u c le ic a c id s " . The discovery that proteins alone can transmit an infectious disease was a considerable surprise to the scientific community. Prion diseases are often called s p o n g if o r m e n c e p h a lo p a t h ie s b e c a u s e o f t h e p o s t m o r t e m a p p e a r a n c e o f t h e b r a i n w i th l a rg e v a c u o l e s i n t h e c o rte x a n d c e re b e l l u m . P ro b ab l y m o s t m a m m a l i a n s p e c i e s d evelo p t hese d iseases. Protein classiﬁcation: "-protein Protein classiﬁcation: !/"-protein Protein classiﬁcation: ! + "-protein nonstandard/modiﬁed amino acids nonstandard & modiﬁed amino acids ...
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This note was uploaded on 08/04/2010 for the course CHM 6620 taught by Professor Dr.christinechow during the Fall '08 term at Wayne State University.
- Fall '08