tema 6 modificaciones postraduccionales
TRANSCRIPT
![Page 1: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/1.jpg)
Nucleolo
Retículo endoplásmico rugoso
Retículo endoplásmico liso
Vesículas de Golgi
Vesículas pequeñas
Membrana plasmática
Mitocondria
Centriolos
Ribosomas
Filamentos del citoesqueleto
.
.
.
.
.
.
.
.
.
..
.
.
PeroxisomaNúcleo
.
.
.
.
Lisosomas
.
![Page 2: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/2.jpg)
![Page 3: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/3.jpg)
![Page 4: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/4.jpg)
![Page 5: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/5.jpg)
![Page 6: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/6.jpg)
Polipéptidos sintetizados nuevos Polipéptidos sintetizados nuevos en la membrana y asociados a RERen la membrana y asociados a RER
⌛Formación de enlaces disulfuro⌛Plegamiento adecuado⌛Adición y procesamiento de CHOs⌛Escisiones proteolíticas específicas⌛Formación complejo multimérico
![Page 7: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/7.jpg)
⌛Proteínas correctamente plegadas/armadas RER ⇒ Complejo Golgi ⇒ Superficie celular u otros
⌛No plegadas o plegadas incorrectamente oparcialmente plegadas o armadas
Retenidas con selectividad en RER o recuperadas desde CIS-Golgi
⌛Mal plegadas o armadas
Retornan del RER a citosol ⇒ degradadas proteasoma
![Page 8: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/8.jpg)
Proteína Disulfuro Isomerasa
PDI
![Page 9: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/9.jpg)
⌘Principal molécula tiólica en eucariotas⌘Impide formación de enlaces disulfuro en citoplasma
GSH:GSSG 50 : 1
NADPH + H+ + GSSG ⇒ NADP+ + 2 GSH
Glutatión reductasa
![Page 10: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/10.jpg)
![Page 11: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/11.jpg)
![Page 12: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/12.jpg)
![Page 13: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/13.jpg)
![Page 14: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/14.jpg)
![Page 15: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/15.jpg)
![Page 16: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/16.jpg)
13 – 36 residuos
hidrofóbicos
![Page 17: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/17.jpg)
![Page 18: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/18.jpg)
Type I: Signal sequence on amino terminus enters first and continues to elongate. Protein is threaded through the translocating channel (open area in rer membrane) until a hydrophobic stop sequence is reached. That hydrophobic stop sequence (seen as a hatched region in the protein) is then inserted in the membrane and forms the anchor for that protein. Signal is cleaved by protease inside the lumen.
![Page 19: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/19.jpg)
Type II: No cleavable signal sequence. These proteins have rather long hydrophobic regions that will be anchored in the membrane. Type II proteins are threaded into the lumen with the C terminus leading. Protein continues to be inserted until it reaches the hydrophobic stop signal sequence.
Type III: Same as Type II, only the N terminus leads into the lumen.
![Page 20: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/20.jpg)
The "positive inside rule" states that amino acid residues nearest the cytosolic side of the hydrophobic anchor sequence are more positive than those nearest the lumenal side. So, whichever end has the least positive charges near the signal anchor patch would go into the ER lumen. One can change the direction of translocation of a protein (reverse it) by mutating the protein and making more positively charged groups near the anchor patch of the other end. Below, the cartoon shows that this can be done to change a Type II protein (COOH end enters ER lumen) to a Type III (which has its amino terminal entering the lumen).
![Page 21: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/21.jpg)
Washburn and Speiss (JCB 137: 555-562, 1997) also tested the length of the hydrophobic signal anchor sequence. The following cartoon shows that a longer hydrophobic anchor sequence (seen as the portion running through the membrane) promotes entry with the amino terminal leading into the lumen.
![Page 22: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/22.jpg)
![Page 23: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/23.jpg)
![Page 24: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/24.jpg)
N – N-
Acetilglucosamina
![Page 25: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/25.jpg)
S –T (OH) N-Acetil-
galactosaminaOH-K
Galactosa
![Page 26: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/26.jpg)
![Page 27: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/27.jpg)
![Page 28: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/28.jpg)
![Page 29: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/29.jpg)
![Page 30: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/30.jpg)
![Page 31: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/31.jpg)
![Page 32: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/32.jpg)
![Page 33: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/33.jpg)
Cis-Golgi
![Page 34: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/34.jpg)
![Page 35: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/35.jpg)
The congenital disorders of glycosilation (CDG) were originally called carbohydrate-deficient glycoprotein syndromes (CDGS) and are a subset of genetic defects affecting primarily N-glycan assembly.
![Page 36: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/36.jpg)
![Page 37: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/37.jpg)
![Page 38: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/38.jpg)
![Page 39: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/39.jpg)
![Page 40: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/40.jpg)
Catepsina D y otras enzimas lisozomales
![Page 41: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/41.jpg)
![Page 42: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/42.jpg)
![Page 43: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/43.jpg)
![Page 44: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/44.jpg)
![Page 45: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/45.jpg)
![Page 46: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/46.jpg)
![Page 47: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/47.jpg)
![Page 48: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/48.jpg)
![Page 49: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/49.jpg)
RER3 min
Aparatp de Golgi20 min
Vesículas secretoras90 min Liberación
120 min
Páncreastritio*
Radio-autografía
![Page 50: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/50.jpg)
![Page 51: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/51.jpg)
RERRER
Cis - GolgiCis - Golgi
Fijación grupo fosfato a manosasen enzimas lisosómicas
evita que sufran nuevos cambios Remueve manosas de
glicoproteínas
.
Red CisRed CisVesículas de transiciónVesículas de transición
Fija manosas N-oligosacáridos (N)
![Page 52: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/52.jpg)
Medial - GolgiMedial - Golgi
Remueve manosas por manosidasas I y II adiciona N-acetilglucosamina por N-acetil-glucosamina transferasa I y II
![Page 53: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/53.jpg)
Trans - GolgiTrans - Golgi
Completa la gricosilación, adición de galactosa y ácido siálico (transferasas) O-oligosacaridos (S/T/HO-K) Liberación de proteínas
Red TransRed TransVesículas de transiciónVesículas de transición
.
![Page 54: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/54.jpg)
![Page 55: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/55.jpg)
![Page 56: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/56.jpg)
![Page 57: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/57.jpg)
![Page 58: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/58.jpg)
![Page 59: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/59.jpg)
![Page 60: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/60.jpg)
Acetilacion
![Page 61: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/61.jpg)
The chemical conversion of arginine to citrulline, known as citrullination or deimination.
These citrulline residues are generated by a family of enzymes called peptidylarginine deiminases (PADs), which convert arginine into citrulline in a process called citrulination or deimination.
![Page 62: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/62.jpg)
![Page 63: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/63.jpg)
![Page 64: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/64.jpg)
Certain proteins are anchored to biological membranes by lipid anchors. Particularly common are the N-myristoyl – and S-palmitoyl – anchoring motifs shown here. N-Myristoylation always occurs at an N-terminal glycine residue, whereas thioester linkages occur at cysteine residues within the polypeptide chain. G-protein – coupled receptors, with seven transmembrane segments, may contain one (and sometimes two) palmitoyl anchors in thioester linkage to cysteine residues in the C-terminal segment of the protein.
![Page 65: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/65.jpg)
Some proteins have lipid moieties attached:
The viral src protein is myristoylated at the N-terminal glycine. Rhodoposin is palmitoylated at a cysteine residue The ras oncogene protein is farnesylated as are some G proteins. Some eukaryotes, notably parasitic protozoa, have glycosylphosphatidylinositol-linked proteins
![Page 66: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/66.jpg)
Proteins containing the C-terminal sequence CAAX can undergo prenylation reactions that place thioether-linked farnesyl or geranylgeranyl groups at the cysteine side chain. Prenylation is accompanied by removal of the AAX peptide and methylation of the carboxyl group of the cysteine residue, which has become the C-terminal residue.
![Page 67: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/67.jpg)
The glycosyl phosphatidylinositol (GPI) moiety is an elaborate lipid-anchoring group. Note the core of three mannose residues and a glucosamine. Additional modifications may include fatty acids at the inositol and glycerol OOH groups.
![Page 68: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/68.jpg)
![Page 69: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/69.jpg)
A two dimensional representation of the Human Aquaporin 0 (AQP0) structure indicating sites of truncation (arrows), sites of deamidation (green residues) and sites of phosphorylation (red diamonds).
![Page 70: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/70.jpg)
Chymotrypsin and trypsin are both synthesized as zymogens. Cleavage of chymotrypsinogen between Arg15 and Ile 16 by trypsin yields the enzymatically active pi-chymotrypsin. Two further proteolytic cleavages catalyzed by chymotrypsin removes the dipeptides Ser14-Arg15 and Thr147-Asn148 to yield alpha-chymotrypsin.
Trypsin is activated by the removal of the N-terminal seven amino acids.
![Page 71: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/71.jpg)
Proteins that require a prosthetic group for activity must have this group added. For example, the haem (heme) group must be added to globins and cytochromes; Fe-S clusters must be added to ferredoxins.
![Page 72: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/72.jpg)
![Page 73: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/73.jpg)
![Page 74: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/74.jpg)
![Page 75: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/75.jpg)
![Page 76: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/76.jpg)
![Page 77: Tema 6 Modificaciones postraduccionales](https://reader035.vdocuments.co/reader035/viewer/2022062220/559344141a28abbb728b4636/html5/thumbnails/77.jpg)
Antes Después Antes Después