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Structure et Fonction des Protéines 2

Structure et Fonction des Protéines 2. 3 crédits 24 heures de cours Amphi 2 12 janvier-> 4 mars 8 heures de TP Bio Cell : 8 / 26 mars Bioch : 29 mars 23 avril Responsable Jean-Pierre Duneau jean-pierre.duneau@univmed.fr. Structure et Fonction des Protéines 2. 3 crédits

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Structure et Fonction des Protéines 2

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  1. Structure et Fonction des Protéines 2 • 3 crédits • 24 heures de cours • Amphi 2 • 12 janvier-> 4 mars • 8 heures de TP • Bio Cell : 8 / 26 mars • Bioch : 29 mars 23 avril • Responsable • Jean-Pierre Duneau • jean-pierre.duneau@univmed.fr

  2. Structure et Fonction des Protéines 2 • 3 crédits • 24 heures de cours (12 jan-> 4 mars)‏ • I Modifications post-traductionnelles des protéines • Pr. Assou El-Battari • 14 heures • Les Mardi à 14h00 + jeudi 4/03 à 8h00 • II Relation Structure-Dynamique-fonction • Jean-Pierre Duneau • 10 heures • Les Jeudi à 8h sauf le 28/01 -> Mercredi 27/01

  3. Maturation structurale et fonctionnelle des protéines 1-Régulation de la traduction des protéines. Rappels 2- Modifications co- et post-traductionnelles La glycosylation 2.1: Les glucides (Rappel) 2.2: La N-glycosylation (modification co-traductionnelle) 2.3: La O-glycosylation (modification post-traductionnelle) 3- Formation des protéoglycanes et glycosaminoglycanes Synthèse de l'héparine et de l'acide hyaluronique 4- Anchrage GPI des protéines membranaires (Glypiation) 5- Autres modifications co- et post-traductionnelles 5.1: Formation des ponts disulfures 5.2: Clivage protéolytique. Exemple des facteurs de coagulation 5.3: Amidation, acylation, sulfatation, phosphorylation

  4. 1- Régulation de la traduction des protéines. Rappels

  5. PP-Dol UDP-GlcNAc Dolicholphosphate N-acétylglucosamine phosphotransférase UMP GlcNAca-PP-Dol UDP-GlcNAc N-acétylglucosaminyl diphosphodolichol N-acétylglucosaminyltransférase UDP GlcNAcb1- 4GlcNAca-PP-Dol CYTOPLASME GDP-Man Dolichol diphosphochitobiose mannosyltransférase GDP Manb1 - 4GlcNAcb1- 4GlcNAca-PP-Dol 4(GDP-Man) Glycolipide a-mannosyltransférases 4GDP Mana1 Mana1 - 2Mana1 6 Manb1 - 4GlcNAcb1 - 4GlcNAca-PP-Dol 3 Mana1 – 2Mana1 Dol-P-Man glycolipide a-mannosyltransférase Flippase Mana1 - 2Mana1 6 Mana1 3 Glycolipide a-glucosyltransférase RETICULUM 6 Manb1 - 4GlcNAcb1 - 4GlcNAca-PP-Dol 3 Mana1 - 2Mana1 Glca1 - 2Glca1 - 3Glca1 - 3Mana1 - 2Mana1 - 2Mana1

  6. P-Dol UDP-GlcNAc Dolicholphosphate N-acétylglucosamine phosphotransférase UMP GlcNAca-PP-Dol UDP-GlcNAc N-acétylglucosaminyl diphosphodolichol N-acétylglucosaminyltransférase UDP GlcNAcb1- 4GlcNAca-PP-Dol GDP-Man Dolichol diphosphochitobiose mannosyltransférase GDP cytoplasme Manb1 - 4GlcNAcb1- 4GlcNAca-PP-Dol 4(GDP-Man) Glycolipide a-mannosyltransférases 4GDP RE Mana1 6 Manb1 - 4GlcNAcb1 - 4GlcNAca-PP-Dol 3 lumière Mana1 - 2Mana1 - 2Mana1 4(Manb-P-Dol) Dol-P-Man glycolipide a-mannosyltransférase Mana1 – 2Mana1 4Dol-P 6 Mana1 3 6 Manb1 - 4GlcNAcb1 - 4GlcNAca-PP-Dol 3 Mana1 - 2Mana1 Mana1 - 2Mana1 - 2Mana1 3(Glcb-P-Dol) Glycolipide a-glucosyltransférase 3Dol-P Mana1 - 2Mana1 6 Mana1 3 6 Manb1 - 4GlcNAcb1 - 4GlcNAca-PP-Dol 3 Mana1 - 2Mana1 Glca1 - 2Glca1 - 3Glca1 - 3Mana1 - 2Mana1 - 2Mana1 Peptide-(Asn-X-Ser/Thr) oligosaccharidyltransférase Mana1 - 2Mana1 PP-Dol 6 Mana1 3 6 Manb1 - 4GlcNAcb1 - 4GlcNAcb-Asn.peptide 3 Mana1 - 2Mana1 Glca1 - 2Glca1 - 3Glca1 - 3Mana1 - 2Mana1 - 2Mana1 R Mannosyl-oligosaccharide a-glucosidase I 1 Glc a-glucosidase II 1 Glc UDP-Glc:a1,3glucosyltransférase Mana1 - 2Mana1 Mana1 - 2Mana1 UDP UDP-Glc 6 Mana1 3 6 Mana1 3 6 Manb1 - R 3 6 Manb1 - R 3 Mana1 - 2Mana1 Mana1 - 2Mana1 Glc Glca1 - 3Mana1 - 2Mana1 -2Mana1 Mana1 - 2Mana1 - 2Mana1 a-glucosidase II Mana1 - 2Mana1 Mannosyl-oligosaccharide 1,2-a-mannosidase IA 1 Man 6 Mana1 3 6 Manb1 - R 3 Mana1 Mana1 - 2Mana1 - 2Mana1 Figure 1 : Biosynthèse des N-glycannes dans le RE

  7. Golgi ERp57 (disulphide isomerase) protein folding on/off calnexin cx G II P a-glucosidase II ERGIC-53 EDEM P glucosyl- transferase mannosidase P other chaperones ER Glc EDEM P Glc a-glucosidase I & II Glc Man Man P Sec61 proteasome

  8. GnT V GlcNAcb1 6 4 Mana1 3 GnT VI GlcNAcb1 GlcNAcb1 GnT II 6 4Manb1 - 4GlcNAcb1 - 4GlcNAcb1 - Asn 3 GlcNAcb1 GnT III GlcNAcb1 GnT IV 6 4 Mana1 3 GnT I GlcNAcb1

  9. Mana1 6 Mana1 3 Mana1 6 Manb1 - R 3 6 Manb1  R 3 Mana1 Mana1 Mana1 Mana1 6 Mana1 3 Mana1 6 Mana1 3 Fuca1 Fuca1 6 GlcNAcb1- 4Manb1 - R,R ’ 3 Mana1 6 Manb1 - R 3 6 4GlcNAcb1- 4GlcNAcb-Asn-peptide. 6 4GlcNAcb1- 4GlcNAcb-Asn-peptide Mana1 GlcNAcb1-2Mana1 GlcNAcb1-2Mana1 Mana1 Mana1 6 GlcNAcb1- 4Manb1 - R,R ’ 3 6 Manb1 - R,R ’ 3 Mana1 6 Manb1 - R,R ’ 3 GlcNAcb1-2Mana1 GlcNAcb1-2Mana1 GlcNAcb1 4 Mana1 2 GlcNAcb1 GlcNAcb1-2Mana1 GlcNAcb1-2Mana1 6 GlcNAcb1- 4Manb1 - R,R ’ 3 6 Manb1 - R, R ’ 3 GlcNAcb1-2Mana1 GlcNAcb1-2Mana1 GlcNAcb1 GlcNAcb1 6 Mana1 2 6 Mana1 2 GlcNAcb1-2Mana1 GlcNAcb1- 2Mana1 GlcNAcb1 6 GlcNAcb1- 4Manb1 - R,R ’ 3 6 Manb1  R,R ’ 3 6 GlcNAcb1- 4Manb1 - R,R ’ 3 6 Manb1 - R,R ’ 3 GlcNAcb1 GlcNAcb1 GlcNAcb1 4 Mana1 2 4 Mana1 2 GlcNAcb1-2Mana1 GlcNAcb1-2Mana1 GlcNAcb1 GlcNAcb1 GlcNAcb1 GlcNAcb1 6 GlcNAcb1 - 4Mana1 2 GlcNAcb1 6 Mana1 2 GlcNAcb1 6 Mana1 2 6 GlcNAcb1- 4Mana1 2 6 GlcNAcb1 - 4Manb1 - R,R ’ 3 GlcNAcb1 6 GlcNAcb1- 4Manb1 - R,R ’ 3 GlcNAcb1 6 Manb1 - R,R ’ 3 GlcNAcb1 6 Manb1 - R,R ’ 3 GlcNAcb1 GlcNAcb1 GlcNAcb1 GlcNAcb1 4 Mana1 2 GlcNAcb1 4 Mana1 2 4 Mana1 2 4 Mana1 2 GlcNAcb1 GlcNAcb1 GlcNAcb1 GlcNAcb1 Mana1 - 2Mana1 6 Mana1 3 6 Manb1 - R 3 Mana1 Mana1 - 2Mana1 - 2Mana1 Mannosyl-oligosaccharide1,3-1,6-a-mannosidase III Mannosyl-oligosaccharide 1,2-a-mannosidase IB GnT I Glycoprotéine-6-a-L-fucosyltransférase GnT III R ’ Mannosyl-oligosaccharide1,3-1,6-a-mannosidase II GnT III GnT I GnT IV GnT II GnT III GnT IV GnT V GnT III GnT III GnT IV GnT V GnT III GnT III GnT VI Figure 4 : Action des GnTs dans la biosynthèse des N-glycannes. R= 4GlcNAcb1 -4GlcNAcb-Asn.peptide, R ’=

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