Proteopedia

Hox protein: Difference between revisions

← Older edit
No edit summary
Michal Harel (talk | contribs)
31,761 edits
No edit summary
 
(13 intermediate revisions by 4 users not shown)
Line 1: Line 1:
<StructureSection load='2r5z' size='410' side='right' scene='Sandbox_Reserved_169/Complex/1' caption=''>
{{BAMBED
|DATE=July 20, 2012
|OLDID=1419976
|BAMBEDDOI=10.1002/bmb.20650
}}
<StructureSection load='' size='350' side='right' scene='Sandbox_Reserved_169/Complex/1' caption='Homeotic protein SEX complex with homeobox protein extradenticle and DNA (PDB code [[2r5z]]).'>
''This is a joint project of students at La Cañada High School, La Cañada Flintridge, California USA, and students at the University of Southern California, Los Angeles, California USA, mentored by [[User:Remo Rohs|Professor Remo Rohs]].''
''This is a joint project of students at La Cañada High School, La Cañada Flintridge, California USA, and students at the University of Southern California, Los Angeles, California USA, mentored by [[User:Remo Rohs|Professor Remo Rohs]].''


Line 10: Line 15:
[[Image:Cell.jpg|thumb|right|300px|Figure 2: Hox proteins require a cofactor to achieve high binding specificity in order to execute their distinct functions in developing various parts of the fly embryo. Elsevier/Cell Press has provided permission for usage of this figure<ref name="slattery">Slattery M, Riley T, Liu P, Abe N, Gomez-Alcala P, Dror I, Zhou T, Rohs R, Honig B, Bussemaker HJ, Mann RS. Cofactor binding evokes latent differences in DNA binding specificity between Hox proteins. Cell. 2011;147(6):1270-82. [http://www.ncbi.nlm.nih.gov/pubmed/22153072 PMID:22153072]</ref>.]]
[[Image:Cell.jpg|thumb|right|300px|Figure 2: Hox proteins require a cofactor to achieve high binding specificity in order to execute their distinct functions in developing various parts of the fly embryo. Elsevier/Cell Press has provided permission for usage of this figure<ref name="slattery">Slattery M, Riley T, Liu P, Abe N, Gomez-Alcala P, Dror I, Zhou T, Rohs R, Honig B, Bussemaker HJ, Mann RS. Cofactor binding evokes latent differences in DNA binding specificity between Hox proteins. Cell. 2011;147(6):1270-82. [http://www.ncbi.nlm.nih.gov/pubmed/22153072 PMID:22153072]</ref>.]]
{{Clear}}
{{Clear}}
Hox proteins are transcription factors that play a key role in the '''embryonic development''' across species by activating and repressing genes. In ''Drosophila,'' eight Hox proteins are responsible for the development of different body segments of the fly, such as its antennae, wings, or legs. Hox proteins execute their distinct functions through binding to similar but different in vivo binding sites<ref>Mann RS, Lelli KM, Joshi R. Hox specificity unique roles for cofactors and collaborators. Curr Top Dev Biol. 2009;88:63-101. [http://www.ncbi.nlm.nih.gov/pubmed/19651302 PMID:19651302]</ref>. This page discusses molecular mechanisms through which Hox proteins recognize their DNA targets with very high binding specificity. <br/>
'''Hox proteins''' or '''homeobox proteins''' are transcription factors that play a key role in the '''embryonic development''' across species by activating and repressing genes. In ''Drosophila,'' eight Hox proteins are responsible for the development of different body segments of the fly, such as its antennae, wings, or legs. Hox proteins execute their distinct functions through binding to similar but different in vivo binding sites<ref>Mann RS, Lelli KM, Joshi R. Hox specificity unique roles for cofactors and collaborators. Curr Top Dev Biol. 2009;88:63-101. [http://www.ncbi.nlm.nih.gov/pubmed/19651302 PMID:19651302]</ref>. This page discusses molecular mechanisms through which Hox proteins recognize their DNA targets with very high binding specificity. <br/>


The crystal structure of a Hox-DNA complex (Figure 1) shows that the Hox protein ''Sex combs reduced'' (Scr) binds its specific ''in vivo'' site with the help of cofactors, ''Extradenticle (Exd)/Pbx proteins''. Hox proteins can bind DNA as monomers but their binding specificity is enhanced when the co-factor is present, a principle that is called '''latent specificity''' (Figure 2). In ''Drosophila'', for instance, eight Hox proteins bind as heterodimers with their cofactor Exd to similar but distinct target sites.<br/>
The crystal structure of a Hox-DNA complex (Figure 1) shows that the Hox protein ''Sex combs reduced'' (Scr) binds its specific ''in vivo'' site with the help of cofactors, ''Extradenticle (Exd)/Pbx proteins''. Hox proteins can bind DNA as monomers but their binding specificity is enhanced when the co-factor is present, a principle that is called '''latent specificity''' (Figure 2). In ''Drosophila'', for instance, eight Hox proteins bind as heterodimers with their cofactor Exd to similar but distinct target sites.<br/>
Line 59: Line 64:
==High-throughput Analysis of Hox-DNA Binding Specificity==
==High-throughput Analysis of Hox-DNA Binding Specificity==


[[Image:Slattery-etal-Figure6.jpg‎ |thumb|right|300px|Figure 7:  DNA shape analysis of >650,000 sites derived from SELEX-seq experiments. Elsevier/Cell Press has provided permission for usage of this figure<ref name="slattery"/>.]]
[[Image:Slattery-etal-Figure6.jpg‎ |thumb|right|300px|Figure 7:  DNA shape
{{Clear}}
Based on SELEX-seq data and a method for high-throughput prediction of DNA shape, the same pattern of two minima in minor groove width (A) was predicted for the binding sites of all anterior Hox proteins vs. a single minimum (A) for all posterior Hox proteins (dark green for narrow groove, white for wide groove). Frames highlight the regions that correspond to the minima in Figure 6. Differences in minor groove width between binding sites can be visualized in a Euclidean distance dendrogram, which forms two branches representing anterior and posterior Hox proteins (B). The differences between both groups are significant as shown by Pearson correlation (C). Remarkably, using DNA shape of their selected binding sites the eight ''Drosophila'' Hox proteins order according to their collinearity. This result, thus, indicates how Hox genes have likely differentiated throughout evolution.<br/>


=Further Reading=
==3D structure of Hox protein==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}


See also within Proteopedia:
[[1b72]] – hHox-B1 + DNA – human<br />
* [[P53-DNA Recognition]] which involves Hoogsteen base pairing.
[[1puf]] – hHox-PRL + mHox-A9 + DNA <br />
* [[Lac repressor]] which shows kinked and bent DNA, the former stabilized by lac repressor binding, and a morph between straight and kinked DNA.
[[2l7z]] – hHox-A13 + DNA – NMR<br />
* [[Transcription and RNA Processing]] which lists Proteopedia articles about transcription factors.
[[2lp0]] – hHox-A13 + geminin peptide – NMR<br />
[[2cra]] – hHox-B13 – NMR<br />
[[5edn]], [[5eea]], [[5ef6]], [[5no6]] – hHox-B13 + DNA<br />
[[5eg0]], [[5ego]] – hHox-B13 + MEISI1 + DNA<br />
[[2msy]] – hHox-C9 – NMR<br />
[[3a03]] – hHox-11L1<br />
[[1ig7]] – mHox-MSX + DNA – mouse<br />
[[1lfu]] – mHox-PBX + DNA – NMR<br />
[[2ld5]] – mHox-A13 + DNA – NMR<br />
[[4uut]] – DmHox – ''Drosophila melanogaster''<br />
[[2r5z]] – DmHox + DNA <br />
[[2r5y]] – DmHox + Scr + DNA <br />
[[4uus]], [[5cyc]] – DmHox + Ubx+ DNA <br />
[[5zjq]], [[5zjr]], [[5zjs]], [[5zjt]] – DmHox + AbdB+ DNA <br />


A more general discussion of structural origins of binding specificity in protein-DNA recognition has been published along with a suggestion for a new '''classification of protein-DNA readout modes''' that goes beyond the historical description of direct and indirect readout<ref name="annualreview">Rohs R, Jin X, West SM, Joshi R, Honig B, Mann RS. Origins of specificity in protein-DNA recognition. Annu Rev Biochem. 2010;79:233-69. [http://www.ncbi.nlm.nih.gov/pubmed/20334529 PMID:20334529]</ref>.<br/>
== References ==
 
<references/>
=Acknowledgements=
This Proteopedia page originates from the partnership of the Rohs Laboratory at the University of Southern California with La Cañada High School. This partnership was initiated by Remo Rohs and Patty Compeau in September 2011 as '''Bioinformatics Institute''', which is part of the Institutes of the 21st Century. Advice and technical help by Proteopedia editors Eran Hodis, Eric Martz, Jaime Prilusky, and Joel Sussman is acknowledged. Eric Martz provided technical assistance, especially with [[Help:Color Keys|color keys in the text]], but did not write any of the scientific content of this article.


=References=
[[Category:Featured in BAMBED]]
<references/>
[[Category:Topic Page]]
Retrieved from "https://proteopedia.openfox.io/w/Hox_protein"