Revisión como estaba o 6 de xaneiro de 2016 ás 17:18 editar Miguelferig (conversa \| contribucións) 242.260 edicións →‎Importancia médica ← Edición máis vella		Revisión como estaba o 6 de xaneiro de 2016 ás 18:00 editar desfacer Miguelferig (conversa \| contribucións) 242.260 edicións →‎Unión a ciclinas Edición máis nova →
Liña 108: === Unión a ciclinas === <!--▼ The active site, or ATP-binding site, of all kinases is a cleft between a small amino-terminal lobe and a larger carboxy-terminal lobe.<ref name = "Morgan2007" /> The structure of human Cdk2 revealed that CDKs have a modified ATP-binding site that can be regulated by cyclin binding.<ref name = "Morgan2007" /> Phosphorylation by CDK-activating kinase (CAK) at Thr 161 on the T-loop increases the complex activity. Without cyclin, a flexible loop called the activation loop or T-loop blocks the cleft, and the position of several key amino acid residues is not optimal for ATP-binding.<ref name = "Morgan2007" /> With cyclin, two alpha helices change position to permit ATP binding. One of them, the L12 helix that comes just before the T-loop in the primary sequence, becomes a beta strand and helps rearrange the T-loop, so it no longer blocks the active site.<ref name = "Morgan2007" /> The other alpha helix called the PSTAIRE helix rearranges and helps change the position of the key amino acid residues in the active site.<ref name = "Morgan2007" /> O [[sitio activo]], ou sitio para a unión do ATP, de todas as [[quinase]]s é unha fenda situada entre un pequeno lobo [[amino terminal]] e outro meirande [[carboxi terminal]].<ref name = "Morgan2007" /> A estrutura da Cdk2 humana indica que as CDKs teñen un sitio de unión ao ATP modificado que pode ser regulado pola unión de ciclinas.<ref name = "Morgan2007" /> A fosforialción pola quinase activadora de CDK (CAK) da [[treonina\|Thr]] 161 do bucle T incrementa a actividade do complexo. Sen ciclina, un bule flexible chamado o bucle de activación ou bucle T bloquea a fenda, e a posición de varios residuos de aminoácidos clave non é a óptima para a unión do ATP.<ref name = "Morgan2007" /> Coa ciclina, dúas hélices alfa cambian de posioción para permitir a unión do ATP. Unha delas, a [[hélice alfa\|hélice]] L12 que está xusto despois do bucle T na [[secuencia primaria das proteínas\|secuencia primaria]], convértese nunha [[folla beta]] e axuda a rearranxar o bucle T, polo que este xa non bloquea o sitio activo.<ref name = "Morgan2007" /> A outra hélice alfa chamada hélices PSTAIRE rearranxa e axuda a cambiar a posición de residuos de aminoácidos clave no sitio activo.<ref name = "Morgan2007" /> There is considerable specificity in which cyclin binds with CDK.<ref name = "Morgan1997">Morgan, David O. (1997) "Cyclin-Dependent Kinase: Engines, Clocks, and Microprocessors." ''Annual Review of Cell and Developmental Biology.'' 13:261-291.</ref> Furthermore, cyclin binding determines the specificity of the cyclin-CDK complex for particular substrates.<ref name = "Morgan1997" /> Cyclins can directly bind the substrate or localize the CDK to a subcellular area where the substrate is found. Substrate specificity of S cyclins is imparted by the hydrophobic batch (centered on the MRAIL sequence), which has affinity for substrate proteins that contain a hydrophobic RXL (or Cy) motif. Cyclin B1 and B2 can localize Cdk1 to the nucleus and the Golgi, respectively, through a localization sequence outside the CDK-binding region.<ref name = "Morgan2007" /> A unión da ciclina coa CDK presenta unha considerable especificidade.<ref name = "Morgan1997">Morgan, David O. (1997) "Cyclin-Dependent Kinase: Engines, Clocks, and Microprocessors." ''Annual Review of Cell and Developmental Biology.'' 13:261-291.</ref> Ademais, a unión da ciclina determina a especificidade do complexo ciclina-CDK por substratos particulares.<ref name = "Morgan1997" /> As ciclinas poden unirse directamente ao substrato ou localizan a CDK nunha área subcelular na que se encontra o substrato. A especificidade de substrato das ciclinas S débese ao lote hidrofóbico (centrado na secuencia MRAIL), que ten afinidade por proteínas substrato que conteñen un motivo RXL hidrofóbico (ou Cy). As ciclinas B1 e B2 poden localizar a Cdk1 no [[núcleo celular\|núcleo]] e no [[complexo de Golgi]], respectivamente, por medio dunha secuencia de localización situada fóra da rexión de unión á CDK.<ref name = "Morgan2007" /> ~~===Phosphorylation===~~ === Fopsforilación === ▲<!-- Full [[kinase]] activity requires an activating [[phosphorylation]] on a [[threonine]] adjacent to the [[active site]].<ref name = "Morgan2007" /> The identity of the CDK-activating kinase (CAK) that performs this phosphorylation varies across the model organisms.<ref name = "Morgan2007" /> The timing of this phosphorylation varies as well. In mammalian cells, the activating phosphorylation occurs after cyclin binding.<ref name = "Morgan2007" /> In yeast cells, it occurs before cyclin binding.<ref name = "Morgan2007" /> CAK activity is not regulated by known cell-cycle pathways and cyclin binding is the limiting step for CDK activation.<ref name = "Morgan2007" /> Liña 141: Proteins with no homology to the cyclin family can be direct activators of CDKs.<ref name = "ringo">Mouron, Silvana; de Carcer, Guillermo; Seco, Esther; Fernandez-Miranda, Gonzalo; Malumbres, Marcos; Nebreda, Angel. (2010). "RINGO C is required to sustain the spindle assembly checkpoint." ''Journal of Cell Science.'' 123:2586-2595.</ref> One family of such activators is the RINGO/Speedy family,<ref name = "ringo" /> which was originally discovered in Xenopus. All five members discovered so far directly activate Cdk1 and Cdk2, but the RINGO/Speedy-CDK2 complex recognizes different substrates than cyclin A-CDK2 complex.<ref name = "noncyclin" /> --> == Historia== [[Leland H. Hartwell]], [[R. Timothy Hunt]], e [[Paul M. Nurse]] recibiron o [[Premio Nobel de Medicina ou Fisioloxía]] de 2001 pola completa descrición que fixeron das [[ciclina]]s e mecanismos das quinases depenentes de ciclinas, que son básicos para a regulación do ciclo celular.

Quinase dependente de ciclina: Diferenzas entre revisións