cyclins: a structure and function anna ajduk, hulya cabadak, karolina czaja, heli honkala, stephen...
TRANSCRIPT
Cyclins: a structure and
function
Anna Ajduk, Hulya Cabadak, Karolina Czaja, Heli Honkala,
Stephen Huisman
Introduction
Conserved domains and motifs
AAMTPHDFIEHFLSKMPEADENKQTIRKH-------AQTFVALCATDVKFISNPPSMVAA AAVTPHDFIEHILRKLPQQKEKLSLIRKH-------AQTFIALCATDFKFAMYPPSMIAT AAVIAHDFLALILHRLSLPSDRQALVKKH-------AQTFLALCATDYTFAMYPPSMIAT AAPTVNQFLTQYFLHLQPANCKVESLAMF-------LGELSLIDAD--PYLKYLPSLIAG GRPLPLHFLRRAS-KVGEVDVEQHTLAKY-------LMELSMLDYD---MVHFAPSQIAA SPLTIVSWLNVYVQVAYVNDTGEVLMPQYPQQVFVQIAELLDLCVLDVGCFRFPYGVLAA
cyclinD1 1 -----------------------------------------------MEHQLLCCE-VET cyclinD2 1 -------------------------------------------------MELLCCE-VDP cyclinD3 1 -------------------------------------------------MELLCCEGTRH cyclinA 1 KTRRVAPLKDLPINDEHVTAGPSWKAVSKQPAFTIHVDEAEETQKRPAELKETECEDALA cyclinB1 1 PLKREAKTLGTGKGTVKALPKPVEKVPVCEPEVELAEPEPEPELEHVREEKLSPEPILVD cyclinE 1 KIDKTVKSEDS--------SQPWDDNSACVDPCSFIPTPNKEEDNELEYPRTAFQPRKIR
TEETCAPSVSYFKCVQKEIVPSMRKIVATWMLEVCEEQKCEEEVFPLAMNYLDRFLSLEP IEERYLPQCSYFKCVQKDIQPYMRRMVATWMLEVCEEQKCEEEVFPLAMNYLDRFLAGVP LEERYVPRASYFQCVQKEIKPHMRKMLAYWMLEVCEEQRCEEDVFPLAMNYLDRYLSCVP MEVKCKPKVGYMK-RQPDITNSMRAILVDWLVEVGEEYKLQNETLHLAVNYIDRFLSSMS LEEEQSVRPKYLQ--GREVTGNMRAILIDWLIQVQMKFRLLQETMYMTVSIIDRFMQNSC NKEKTYLRDEHFLQRHPLLQARMRAVLLDWLMEVCEVYKLHRETFYLAQDFFDRYMASQQ
GSVVAAMQGLNLGSPN-----------------NFLSCYRTTHFLSRVIKCDPDCLRACQ GSVGAAICGLQQDDEV-----------------NTLTCDALTELLAKITHTDVDCLKACQ GSIGAAVLGLGACS---------------------MSADELTELLAGITGTEVDCLRACQ AAFHLALY--------------------------TVTGQSWPESLAQQTGYTLESLKPCL GAFCLALK--------------------------ILDNGEWTPTLQHYLSYSEDSLLPVM SALYHFSSLELMQKVSGYQWCDIEKCVKWMVPFAMVIREMGSSKLKHFRGVPMEDSHNIQ
-LKKSRLQLLGATCMFVASKMKETIPLTAEKLCIYTDNSIRPEELLQMELLLVNKLKWNL -TPKTHLQLLGAVCMFLASKLKETIPLTAEKLCIYTDNSVKPQELLEWELVVLGKLKWNL -TRKAQLQLLGTVCLLLASKLRETTPLTIEKLCIYTDQAVAPWQLREWEVLVLGKLKWDL -VLRGKLQLVGTAAMLLASKFEEIYPPEVAEFVYITDDTYSKKQVLRMEHLVLKVLAFDL -VPKKMLQLVGVTAMFIASKYEEMYPPEIGDFAFVTNNTYTKHQIRQMEMKILRVLNFSL NIIKTLLQLIGISALFIASKLEEIYPPKLHQFAYVTDGACSGDEILTMELMMMKALKWRL
EQIEALLESSLRQAQQNVDPKATEEE-------------GEVEEEAGLACTPTDVRDVDI EQIEALLLNSLQQFRQEQHNAGSKS-----------------VEDPDQATTPTDVRDVDL EQIEAALRESLREAAQTAPSPVPKAPR------------GSSSQGPSQTSTPTDVTAIHL VDLHQTYLKAPQHAQQSIREKYKHS-----------------KYHSVSLLNPPETLSV-- QHLAKNVVMVNCGLTKHMTVKNKYAAS------------KHAKISTLAQLNCTLVQNLSK THTNSLDLLDKAQAKKAILSEQNRISPPPSVVLTPPPSSKKAEQRAGDRMTKPAIASKDS
------------------------------------------------------------ ------------------------------------------------------------ ------------------------------------------------------------ ------------------------------------------------------------ AVTKA------------------------------------------------------- GVEAAAWSSLCCLGGQEPLQMLCSMERCISSGAAGVCKMPWMEVLLLNARCFNYRVKYTS
------------ ------------ ------------ ------------ ------------ HLQNTTECSRSC
IRRAY--------------------PDTNLLND-RVLRA------------------MLK VRRAV--------------------PDRNLLED-RVLQN------------------LLT APRAG--------------------PDPRLLGDQRVLQS------------------LLR FNAAVSLPAARKPLTPLDYPMDGSFESPHAMDMSIVLEDKPVNVNEVPDYQEDIHTYLRE NPSPSPMETSG---CAPAEEYLCQAFSDVILAVSDVDADDGADPNLCSEYVKDIYAYLRQ PPRASP------------------LPVLNWGNREEVWR-------------------IML
cyclin-boxN C
N-domain(5 helices)
C-domain(5 helices)
R - x(2) - [LIVMSA] - x(2) - [FYWS] - [LIVM] - x(8) - [LIVMFC] - x (4) - [LIVMFYA] - x(2) - [STAGC] - [LIVMFYQ] - x - [LIVMFYC] - [LIVMFY] - D - [RKH] - [LIVMFYW]
Structure of mouse cyclin B1
Cyclins bind with cyclin-depended kinases (CDKs) and activate them:
CycA – CDK 2CycB – CDK1
CycD – CDK 4,5CycE – CDK2
cycCDK
Cyclins bind with CDKs
Crystal structure ofcycA1 and CDK2
Model of cycB1 and CDK1
Cyclins are regulated by phosphorylation
S90 S197
S234 T287cycD1
PKA GSK-3
turnovercontrol
G1/S progression
S126 S128
S133 S147cycB1
PLK
MAPK
nuclear localisation
phosphorylation by Plk
S- and M-phase cyclins contain a destruction box
PAATSKPGLRPRTALGDIGNKVS VTAASKPGLRPRTALGDIGNKVS -VVATKPGLRPRTALGDIGNKA- AAPVQQPRTRAALAVLKSGNPRG LAPAQQPR---AQAVLKAGNVRG
RTALGDIGN
RAALAVLKSGN
Hum-cycB1Mou-cycB1Xen-cycB1Hum-cycA2Mou-cycA2
proteolysis cyc
Phylogenetic comparison
Thank you, Tesekkurler, Dziekujemy,Kiitos, Bedankt
Hulya
Karolina
AnnaHeli
Stephen