general:
Activators - protein-DNA interaction
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The sequence specific activators: transcription factors Modular design with a minimum of two
functional domains 1. DBD - DNA-binding domain 2. TAD - transactivation domain
DBD: several structural motifs classification into TF-families
TAD - a few different types Three classical categories
Acidic domains (Gal4p, steroid receptor) Glutamine-rich domains (Sp1) Proline- rich domains (CTF/NF1)
Mutational analyses - bulky hydrophobic more important than acidic Unstructured in free state - 3D in contact with target?
Most TFs more complex Regulatory domains, ligand binding domains etc
N
C
TAD
DB
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TF classification based on structure of DBD
bHelix-Loop-Helix(Max)
Zinc finger
Leucine zipper(Gcn4p)
p53 DBDNFκB
STATdimer
Two levels of recognition1. Shape recognition
An α−helix fits into the major groove in B-DNA. This is used in most interactions
2. Chemical recognitionNegatively charged sugar-phosphate chain involved in electrostatic interactionsHydrogen-bonding is crucial for sequence recognition
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Alternative classification of TFs on the basis of their regulatory role Classification questions
Is the factor constitutive active or requires a signal for activation? Does the factor, once synthesized, automatically enter the nucleus to act
in transcription? If the factor requires a signal to become active in transcriptional
regulation, what is the nature of that signal? Classification system
I. Constitutive active nuclear factors II. Regulatory transcription factors
Developmental TFs Signal dependent
Steroid receptors Internal signals Cell surface receptor controlled
Nuclear Cytoplasmic
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Classification - regulatory function
Brivanlou and Darnell (2002) Science 295, 813 -
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Sequence specific DNA-binding- essential for activators TFs create nucleation sites in promoters for
activation complexes Sequence specific DNA-binding crucial role
Principles of sequence specific DNA-binding
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How is a sequence (cis-element) recognized from the outside?
Electrostaticinteraction
Hydrophobicinteraction
Hydrogen-bonds
Form/geometry
Shape recognition Chemical recognition
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Complementary forms
The dimension of an α−helix fits the dimensions of the major groove in B-DNA
Sidechains point outwards and are ideally positioned to engage in hydrogen bonds
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Direct reading of DNA-sequenceRecognition of form
The dimension of an α-helix fits the dimensions of the major groove in B-DNA
Most common type of interaction
Usually multiple domains participate in recognition dimers of same motif tandem repeated motif Interaction of two different motifs
recognition: detailed fit of complementary surfaces Hydration /vann participates seq specvariation of DNA-structure
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Example
Steroid receptor
434 fag repressor
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DNAs form:B-DNA most common
B-form
Major Minor
wide geometryfits α-helix
Each basepair with unique H-bonding-
pattern
Deep and narrow geometry
Each basepairbinary H-bonding-
pattern
B
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DNAs form:A-form more used in RNA-binding
A-form
Major Minor
Deep and narrow geometry Wide and shallow
A
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How is a sequence (cis-element) recognized from the outside?
Electrostaticinteraction
Hydrophobicinteraction
Hydrogen-bonds
Form/geometry
Shape recognition Chemical recognition
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Next level: chemical recognition - reading of sequence information Negatively charged
sugar-phosphate chain = basis for electrostatic interaction Equal everywhere - no sequence-
recognition Still a main contributer to the
strength of binding
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Odd S. Gabrielsen
Electrostatic interactionEntropy-driven binding
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
- ------
Negative phosphate chainpartially neutralized by acloud of counter ions
Na+
Na+
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
- ------
Counter ions liberatedEntropy-driven binding
MBV4230
Odd S. Gabrielsen
How is a sequence (cis-element) recognized from the outside?
Electrostaticinteraction
Hydrophobicinteraction
Hydrogen-bonds
Form/geometry
Shape recognition Chemical recognition
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Odd S. Gabrielsen
Docked protein side chains exploit the H-bonding possibilities for interaction Hydrogen-bonding is
essential for sequence specific recognition 10-20 x in contact interphase Most contacts in major groove Purines most important
A Zif example
DNA
protein
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Recognition by Hydrogen bonding
A
D A Hydrogen-bonding is a
key element in sequence specific recognition
10-20 x in contact surface
Base pairing not exhausted in duplex DNA, free positions point outwards in the major groove
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Unexploited H-bonding possibilities in the grooves
Point outwards in major groove
Point outwards in minor groove
AT-base pair
GC-base pair
Major groove
Major groove
Minor groove
Minor groove
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Odd S. Gabrielsen
A ”bar code” in the grooves
AT-basepair
GC-basepair
Unique ”bar code” in major groove
DAA
A D A
AT-pair [AD-A] ≠ TA-pair [A-DA]GC-pair [AA-D] ≠ CG-pair [D-AA]
AT-basepair
Binary ”bar code” in minor groove
AA
GC-basepair
AAD
AT-pair [A-A] = TA-pair [A-A]GC-pair [ADA] = CG-pair [ADA]
Unique recognitionof a base pair requiresTWO hydrogen bondsIn the major groove
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Interaction: Protein side chain - DNA bp Close up
Amino acid sidechains points outwards from the α-helix and are optimally positioned for base-interaction
Still no ”genetic code” in the form of sidechain-base rules
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A complex network of H-bonds
Example: c-Myb - DNA Protein
DNA
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How is a sequence (cis-element) recognized from the outside?
Electrostaticinteraction
Hydrophobicinteraction
Hydrogen-bonds
Form/geometry
Shape recognition Chemical recognition
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Hydrophobic contact points
Ile
Homeodomains
HD
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The Homeodomain-family: common DBD-structure
Homeotic genes - biology Regulation of Drosophila development Striking phenotypes of mutants - bodyparts move Control genetic developmental program
Homeobox / homeodomain Conservered DNA-sequence “homeobox” in a large
number of genes Encode a 60 aa “homeodomain” A stably folded structure that binds DNA Similarity with prokaryotic helix-turn-helix
3D-structure determined for several HDs Drosophila Antennapedia HD (NMR) Drosophila Engrailed HD-DNA kompleks (crystal) Yeast MATα2
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Homeodomain-family: common DBD-structure and sequence recognition
Major groove contact via a 3 α-helix structure helix 3 enters major groove
(“recognition helix”) helix 1+2 antiparallel across helix 3 16 α-helical aa conserved
9 in hydrophobic core some in DNA-contact interphase
(common docking mechanism?)
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Engrailed
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Antennapedia
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Homeodomain-family: common DBD-structure
Minor groove contacted via N-terminal flexible arm R3 and R5 in engrailed and R7 in MATα2 contact AT
in minor groove R5 conserved in 97% of HDs Deletions and mutants impair DNA-binding
Loop between helix 1 and 2 determines Ubx versus Antp function Close to DNA exposed for protein protein interaction
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HD-paradox: what determines sequence specificity? Drosophila Ultrabithorax (Ubx), Antennapedia (Antp),
Deformed (Dfd) and Sex combs reduced (Scr): closely similar HD, biological rolle very different
Minor differences in DNA-binding in vitro TAAT-motif bound by most HD-factors contrast between promiscuity in vitro and specific effects in vivo
Swaps reveal that surprisingly much of the specificity is determined by the N-terminal arm which contacts the minor groove Swaps: Antp with Scr-type N-term arm shows Scr-type specificity in vivo Swaps: Dfd with Ubx-type N-term arm shows Ubx-type specificity in vivo
N-terminal arm more divergent than the rest of HD R5 and R7 (contacting DNA) are present in both Ubx, Antp, Dfd, and Scr Other tail aa diverge much more
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Solutions of the paradox
Conformational effects mediated by N-term arm Even if the α-helical HDs are very similar, a much larger diversity is found in
the N-terminal arms that contact the minor groove
Protein-protein interaction with other TFs through the N-terminal arm - enhanced affinity/specificity - the basis of combinatorial control MATα2 interaction with MCM1 - cooperative interactions Ultrabithorax- Extradenticle in Drosophila Hox-Pbx1 in mammals
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Combinatorial TFs give enhanced specificity Hox proteins, such as
Drosophila Ultrabithorax, have low DNA-binding specificity by themselves but gain affinity and specificity when they bind together with the homeoprotein Extradenticle (or Pbx1 in mammals).
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N-tail in protein-protein interaction- adopt different conformations
Mat-α2/Mcm-1HD
HD
β
α
Conformation determinedby prot prot interaction
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The partner may also be a linker histone Repression of the mouse
MyoD gene by the linker histone H1b and the homeodomain protein Msx1.
The first evidence that a linker histone subtype operates in a gene-specific fashion to regulate tissue differentiation
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It works impressively well
Hox genes
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Homeobox families
Hox genes Hox genes govern developmental pathways along the
anterior–posterior axis In mammalian species, there are 39 Hox genes
organised in four clusters labelled A, B, C and D located on four different chromosomes and numbered from 1 to 13, although no cluster contains a full set.
38
POU family
HD HD
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Odd S. Gabrielsen
POU-family: common DBD-structure
The POU-name : Pit-1 pituitary specific TF Oct-1 and Oct-2 lymphoide TFs Unc86 TF that regulates neuronal development in C.elegans
A bipartite160 aa homeodomain-related DBD a POU-type HD subdomain (C-terminally located) et POU-specific subdomain (N-terminally located) Coupled by a variabel linker (15-30 aa)
POU is a structurally bipartite motif that arose by the fusion of genes encoding two different types of DNA-binding domain.
MBV4230
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POU: Two independent subdomains
POUHD subdomain 60 aa closely similar to the classical HD Only weakly DNA-binding by itself (<HD) contacts 3´-half site (Oct-1: ATGCAAAT) docking similar to engrailed. Antp etc Main contribution to non-specific backbone contacts
POUspec subdomain 75 aa POU-specific domain enhances DNA-affinity 1000x contacts 5´-half site (Oct-1: ATGCAAAT) contacts opposite side of DNA relative to HD structure similar to prokaryotic λ- and 434-repressors
The two-part DNA-binding domain partially encircles the DNA.
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Flexible DNA-recognition
POU-domains have intrinsic conformational flexibility and this feature appears
to confer functional diversity in DNA-recognition
The subdomains are able to assume a variety of conformations, dependent on the DNA element.
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Flexibility
On the natural high-affinity Oct-1 octamer (ATGCAAAT) binding site, the two Oct-1 POU-subdomains lie on opposite sides of the DNA
The unstructured linker permits flexible subdomain positioning and hence diversity in Oct-1 sequence recognition.
Myb family TFs
44
HD HD HD
DBD signature
* . :: :: . : * : : : :**::**:::: **.: * ::* .:* .: **:: ***:** :**.*:*:**********:*****:***.*:*::********:**************:***:.*** *** * .*** :********MYBB_HUMAN MSRRTR------CEDLDELHYQDTDSDVPEQR---DSKCKVKWTHEEDEQLRALVRQFGQQDWKFLASHFPNRTDQQCQYRWLRVLNPDLVKGPWTKEEDQKVIELVKKYGTKQWTLIAKHLKGRLGKQCRERWHNHLNPEVKKSCWTEEEDRIICEAHKVLGNRWAEIA 161MYBB_CHICK MARRSR------GEDQDELHCQDTDSDVPEQR---DGRCKVKWTQEEDEQLKMLVRHYGQNDWKFLASHFPNRSDQQCQYRWLRVLNPDLVKGPWTKEEDQKVIELVKKYGTKQWTLIAKHLKGRLGKQCRERWHNHLNPEVKKSSWTEEEDRIIFEAHKVLGNRWAEIA 161 MYB_rat METGPH-----SEDEDDDLQYADHDYEVPQQKGLKKLWNRVKWTRDEDDKLKKLVEQHGTDDWTLIASHLQNRSDFQCQHRWQKVLNPELIKGPWTKEEDQRVIELVQKYGPKRWSLIAKHLKGRIGKQCRERWHNHLNPEVKKSSWTEEEDRIIYEAHKRLGNRWAEIA 165MYBA_HUMAN MAKRSR-----SEDEDDDLQYADHDYEVPQQKGLKKLWNRVKWTRDEDDKLKKLVEQHGTDDWTLIASHLQNRSDFQCQHRWQKVLNPELIKGPWTKEEDQRVIELVQKYGPKRWSLIAKHLKGRIGKQCRERWHNHLNPEVKKSSWTEEEDRIIYEAHKRLGNRWAEIA 165MYBA_CHICK MAKRPR-----TSEEDDDFQYADHDYEISQQRSLKKICNRVKWTRDEDEKLKKLVEQNGTDDWAFIASHLQNRSDFQCQHRWQKVLNPELIKGPWTKEEDQRVIELVQKYGPKRWSLIAKHLKGRIGKQCRERWHNHLNPEVKKSSWTEAEDRVIYEAHKRLGNRWAEIA 165MYBA_XENLA MAGRAR-----SEDEEEDGQFTEHDYDVSLQKGPKKPWSKLRWTKDEDDKVKKLVEKHG-EDWGVVARHFINRSEVQCQHRWHKVLSPELVKGPWTKEEDQRVIELVHKYGPKKWSIIAKHLKGRIGKQCRERWHNHLNPDVKKSSWTEEEDRIIYSAHKRMGNRWAEIA 164 MYB_HUMAN MARRPRHSIYSSDEDDEDFEMCDHDYDGLLPKSGKRHLGKTRWTREEDEKLKKLVEQNGTDDWKVIANYLPNRTDVQCQHRWQKVLNPELIKGPWTKEEDQRVIELVQKYGPKRWSVIAKHLKGRIGKQCRERWHNHLNPEVKKTSWTEEEDRIIYQAHKRLGNRWAEIA 170 MYB_CHICK MARRPRHSIYSSDDDEEDVEMYDHDYDGLLPKAGKRHLGKTRWTREEDEKLKKLVEQNGTEDWKVIASFLPNRTDVQCQHRWQKVLNPELIKGPWTKEEDQRVIELVQKYGPKRWSVIAKHLKGRIGKQCRERWHNHLNPEVKKTSWTEEEDRIIYQAHKRLGNRWAEIA 170 MYB_XENLA MDRRP--SQYSSEEEDDEIEMYEHDYDGLLSK-GKRHLGKTRWTREEDEKLKKLVEQNGTEEWKVIASFLPNRTDVQCQHRWQKVLNPELIKGPWTKEEDQRVIELVHKYGPKRWSVIAKHLKGRIGKQCRERWHNHLNPEVKKSSWTEEEDRTIYEAHKRLGNRWAEIA 167 ruler 1.......10........20........30........40........50........60........70........80........90.......100.......110.......120.......130.......140.......150.......160.......170
*:*******::*******::** : *:*.: . . . . . * : * * .: :MYBB_HUMAN KMLPGRTDNAVKNHWNSTIKRKVDTGGFLSESKDCKPPVYLLLELEDKDGLQSAQPTEGQGSLLTNWPSVPPTIKEEENSEEELAAATTSKEQ--EPIGTDLDAVRTPEPLEEFPKREDQEGSPPETSLPYKWVVEAANLLIPAVGSSLSEALDLIESDPDAWCDLSKFD 329MYBB_CHICK KLLPGRTDNAVKNHWNSTIKRKVDTGGFLNETKESQP-LYLLVEVDDNESQSGTRAES--QTIVPNWPVDISEIKEEDVSDE---EVTGLQELPSELPAADLAEHNEEGTPDDV----VPEDASASVASPYKWVVEAANYLCPTSVPALNEALDMIESDPDGWCDLTQFD 321 MYB_rat KLLPGRTDNSIKNHWNSTMRRKVEQEGYLQDGIKS--ERS-SSKLQHKPCVTEQCKGEIKCDMKKYVGLKYHGRVPWKCEEIPGYQYVSP-------------DGNCVEHVQ-TSAFIQQPFVDED-PDKEKKIKELELLLMSAENEVRRKRLPPQ---PGSFSSWSGSF 314MYBA_HUMAN KLLPGRTDNSIKNHWNSTMRRKVEQEGYLQDGIKS--ERS-SSKLQHKPCAAMD---HMQTQNQFYIPVQ-----------IPGYQYVSP-------------EGNCIEHVQPTSAFIQQPFIDED-PDKEKKIKELEMLLMSAENEVRRKRIPSQ---PGSFSSWSGSF 301MYBA_CHICK KLLPGRTDNSIKNHWNSTMRRKVEQEGYLQDGTKSSSERTGSSTLAQKPCVTME---HLHTQNQFYIPVQT---------HIPVYQYASP-------------EDSCIEHASASANLVQQSFIDDD-PDKEKKIKELELLLMSTENEIRRKRLSSQ---AGSLPGWSGSF 306MYBA_XENLA KLLPGRTDNSIKNHWNSTMKRKVEQEGYLQDLMNC--DRP--SKLQAKSCAAPN---HLQAQNQFYIPVQT---------QIPRYSSLSH-------------DDNCIEIQN-SFSFIQQPFVDADDPEKEKRIKELELLLMSAENEVRRKRVPS-----GSSLTWSESY 299 MYB_HUMAN KLLPGRTDNAIKNHWNSTMRRKVEQEGYLQESSKASQPAVATSFQKNSHLMGFA---QAPPTAQLPATGQPT-----VNNDYSYYHISEAQNVSSHVPYPVALHVNIVNVPQPAAAAIQRHYNDED-PEKEKRIKELELLLMSTENELKGQQVLPTQNHTCSYPGWHSTT 331 MYB_CHICK KLLPGRTDNAIKNHWNSTMRRKVEQEGYLQESSKAGLPSATTGFQKSSHLMAFA---HNPPAGPLPGAGQAP-----LGSDYPYYHIAEPQNVPGQIPYPVALHVNIVNVPQPAAAAIQRHYNDED-PEKEKRIKELELLLMSTENELKGQQALPTQNHTANYPGWHSTT 331 MYB_XENLA KLLPGRTDNAIKNHWNSTMRRKEEQEGYLQNSSKTNQHTIVTNFPKSNHLMTFT---HTRASAEHSQAS---------TSSFPYYHIAEHQNAS----YPVALRVNIVNVPQLATAPVQRHYNDED-PEKEKRIKELELLLMSTENEINQKQEL--LNHTASYTTCHSTT 318 ruler .......180.......190.......200.......210.......220.......230.......240.......250.......260.......270.......280.......290.......300.......310.......320.......330.......340
. : : : : . . : . : :.MYBB_HUMAN LPEEPSAEDSINNSLVQLQASHQQQVLPPRQPSALVPSVTEYRLDGHTISDLSRSSRGELIPISPSTEVGGSGIGTPPSVLKRQRKRRVALSPVTEN------------------------------------------------------------------------- 426MYBB_CHICK LPEEPSAGSSSSSNSPVRQT--------PSKPTPSLPNVTEYRLDGHTISDLSKSRKGELIPISPHAEVS---FGTPPSVLKRQKKRKISLSPVTENA------------------------------------------------------------------------ 408 MYB_rat LMDDSMSN--------------------------TLNNLEEHTTEFYSMDENQTVSAQQN-SPTKFLAVEANAVLSSLQTIPEFAETLELIESDPVAWSDVTSFDLSDAAASPVKSTPVKLMRIQHNEGAMECQFNVSLVLEGKKNSCNGGDSEAIPLASPNVVKFSTPP 457MYBA_HUMAN LMDDNMSN--------------------------TLNSLDEHTSEFYSMDENQPVSAQQN-SPTKFLAVEANAVLSSLQTIPEFAETLELIESDPVAWSDVTSFDISDAAASPIKSTPVKLMRIQHNEGAMECQFNVSLVLEGKKNTCNGGNSEAVPLTSPNIAKFSTPP 444MYBA_CHICK VMEDCVPN--------------------------TLNSLGEQTSEFYSMDETQGTSVQQN-SPTKYLAVEANAVLSSLQTIPEFAETLELIESDPLAWSDVTSFDLSEAVASPVKPAPLKLMRIQHNERAAECQFNVSVMLDGKKHSSISGEEEAVFPTTPNLTKYSTPP 449MYBA_XENLA HMGESMSN--------------------------TMSHLEEQTHDFYSLDEIPNTSGQQS-VEDKILAPEANIVLQPLETIPEFSETLELIDVDTVDWNNIESFELP-FTASPAKHTPMKWI----HEISPECALNSCLVQADGR-----GSASRVLSSSPAMPKFYSPP 432 MYB_HUMAN IADHTRPHGDSA----------------------PVSCLGEHH-STPSLPADPGSLPEESASPARCMIVHQGTILDNVKNLLEFAETLQFIDS----------------------------------------------------------------------------- 401 MYB_CHICK VADNTRTSGDNA----------------------PVSCLGEHHHCTPSPPVDHGCLPEESASPARCMIVHQSNILDNVKNLLEFAETLQLIDS----------------------------------------------------------------------------- 402 MYB_XENLA IGGNPRLHGQST----------------------PDSCLGDPHHSTPSPQVDHSCLPEESASPARYFGVN---LLIQMKNLAEYSET-QLIDS----------------------------------------------------------------------------- 385 ruler .......350.......360.......370.......380.......390.......400.......410.......420.......430.......440.......450.......460.......470.......480.......490.......500.......510
::. : ::: .:****: . :* * .: :: . :*. : ** : : :*:******:** :**:: :. .: **: :*::.*: . :: *MYBB_HUMAN -----------------STSLSFLDSCNSLTPKSTPVKTLPFSPSQFLNFWNKQDTLELESPSLTSTPVCS-QKVVVTTPLHRDKTPLHQKH-AAFVTPDQK-YSMDNTPHTPTPFKNALEK----YGPLKPLPQTP-HLEEDLKEVLRSEAGIELIIEDD--IRPEKQK 569MYBB_CHICK ----------------PSTSLSFLDSCNSMTPKSTPVKTLPFSPSQFLNFWTKQDTLELENPSLTSTPVCS-QKVIVTTPLHRDKTPLLQKN-SAFVTPDQK-YVVDNTPHTPTPFKNALEK----YGPIRPLPQTP-HLEEDLKEVLRSEAGIELIIEDD--VKPHKQK 552 MYB_rat TILRKKKRLRVGQSAGSELGEGSLSEGNNAALKHTPVKTLPFSPSQFFNTCPGSEQLNIENPSFTSTPICG-QKVLITTPLQKEATPKDQKENVGFRTPTIRRSILGTTPRTPTPFKNALAAQEKKYGPLKIVSQPLAFLEEDIREVLKEETGTDIFLKEE---DEPAYK 623MYBA_HUMAN AILRKKRKMRVGHSPGSELRDGSLNDGGNMALKHTPLKTLPFSPSQFFNTCPGNEQLNIENPSFTSTPICG-QKALITTPLHKETTPKDQKENVGFRTPTIRRSILGTTPRTPTPFKNALAAQEKKYGPLKIVSQPLAFLEEDIREVLKEETGTDLFLKEE---DEPAYK 610MYBA_CHICK AILRKKKRLRAGQSPVNELNDGLCNDAINVALKHTPVKTLPFSPSQFFNTCSGNEQFNLENPAFTSTPICG-QKVLITTPLHKETTPTDQKENAGFRTPTIRRSLLGSTPRTPTPFKNALAAQEKKYGPLKLTSQPLAFLEEDIREVLKEETGTDIFLKEE---DDSVYK 615MYBA_XENLA TILRKKK-IHPDLSLTPEVR-----DASNVVLKGTPVKTRQYSPLQLFRSGNVQNHLNLDNLPLTSTPVCG-QKISAT-PLQRQITPKKDKENAGFRTPTIRRSLMAVTPRTPTPFKNALAAQEKKYGPLRTVMQPLIFVEEDIMEVLKKETEKDVFIKEE---KESDCK 591 MYB_HUMAN ----------------------------------------------FLNTSSNHENSDLEMPSLTSTPLIG-HKLTVTTPFHRDQTVKTQKENTVFRTPAIKRSILESSPRTPTPFKHALAAQEIKYGPLKMLPQTPSHLVEDLQDVIKQESDESGIVAEFQENGPPLLK 524 MYB_CHICK ----------------------------------------------FLNTSSNHENLNLDNPALTSTPVCG-HKMSVTTPFHRDQPFKTQKENHVFRTPAIKRSILESSPRTPTPFKNALAAQEIKYGPLKMLPQTPTHLVEDLQDVIKQESEESAIVAGLHESGPPLLK 525 MYB_XENLA ----------------------------------------------FLNTSTQHENLEMEHQSLTSTPICASQKNTITTSLLRDHALRLQKENHLLRTPAIKRSILNSTPRTPTPFKNALAAQEFKHGPLKLLHHTPLHLAEDIQEVIKQETDESGIVHDHCNTEEPLLK 509 ruler .......520.......530.......540.......550.......560.......570.......580.......590.......600.......610.......620.......630.......640.......650.......660.......670.......680
:. * : : : : . . . . : . *. . .:* .: : : *::MYBB_HUMAN RKPGLRRSPIKKVRKSLALDIVDEDVKLMMSTLPKSLSLPTTAPS----NSSSLT-LSGIKE---------DNSLLNQGFLQAKPEKAAVAQKPRSHFTTPAPMSSAWKTVACGGTRDQLFMQEKARQLLG-RLKPSHT-SRTLILS 700MYBB_CHICK RKQGLRRSPIKKVRKSLALDIVDEDMTQNMPALPKTICFKRTQPVNFLSRSLNLS-SSNRKN---------DSGLLNRAFVQVQSEKMSYRKMP-SHFRPPAPMTRAWKAVACGGTQDQLFMQEKARQFLG-TLKQSHT-SRTLILS 686 MYB_rat SCKQEHSASVKKVRKSLALESWDKE-EPGTQLLTEDIS-DMQSENILTTSLLMIPLLEIHDNRCNLTPEKQDINSANKTYTLTKKRPNPNTCKAV-KLEKSLQSNCEWETVVYGKTEDQLIMTEQARRYLSTYTAPSST-SRALIL- 765MYBA_HUMAN SCKQENTASGKKVRKSLVLDNWEKE-ESGTQLLTEDIS-DMQSENRFTTSLLMIPLLEIHDNRCNLIPEKQDINSTNKTYTLTKKKPNPNTSKVV-KLEKNLQSNCEWETVVYGKTEDQLIMTEQARRYLSTYTATSST-SRALIL- 752MYBA_CHICK SCKQEHNSS-KKVRKSLVLDAWEKE-ELGAQLFTEDSGLDVQSENAYTTSLLMIPLLEIHDNRCNLPSENQDTNSSNKANAVIKKKLNACSSKNI-KLEKSLQPNYEWEAVVYGKTEDQLIMTEQARRYLNAYTATSNT-SRALIL- 757MYBA_XENLA PMKQEHVSTVRKVRKSLILDSCDKE-ELGADFLAPDEVSQSQNGNTLPTSFLMIPLGERQDQKC-------DENTDTRKGSVMQRKNYIPATRNV-KLQSSVQPLCEWEAVVYGKTEDQLIMTEQARRYLDTYKPTSSSGLRHLIL- 728 MYB_HUMAN KIKQEVESPTDKSGNFFCSHHWEGD-SLNTQLFTQTSPVADAPN-ILTSSVLMAPASE-------------DEDNVLKAFTVPKNRSLASP---------LQPCSSTWEPASCGKMEEQMTSSSQARKYVNAFSA------RTLVM- 640 MYB_CHICK KIKQEVESPTDKAGNFFCSNHWEGE-NLNTQLFTHASTMEDVPN-LLTSSILKMPVSE-------------EEGSFHKAFAVPRNRPLASP---------MQHLNNAWESASCGKTEDQMALTDQARKYMAAFPT------RTLVM- 641 MYB_XENLA RIKQEVESPTHKVGNLYFSSYWEGE-SLNAQLFRQQSTLDDTSNSILTSSLLMKPVSE-------------KEDHIFKSFPVQSIKSYTSP---------LQHLSGTWDVMSCSRMEDQKILAEQYCKYIKNFS--------TLVI- 624 ruler .......690.......700.......710.......720.......730.......740.......750.......760.......770.......780.......790.......800.......810.......820.......
DBD
TAD
FAETL
TP
EVES
$
$ P
IV.VSBM?
Å Å
K438AcK441Ac
K527$S532Phospho
K503$
Å Å Å
K467Ac K476AcK481Ac
Sano (2001) Tomita (2000)
Versjon 6 -- RAa 7-OCT-2005
OSG et al
W W W W W W W W
W
R1 R2 R3
Trp-rich pseudorepeats
HTH-related motifs3 α-helices in each repeat
R2
R3
3D DBD
R2 R3
c-Myb
DNA-binding domainControls blood cell development
Subject to oncogenic activation