Analysis of the Kluyveromyces lactis Heat Shock Factor:
A Representative of the Helix-Turn-Helix
Transcription Factor Family





SUMMARY

DISEASE

FAMILY

FUNCTION

STRUCTURE

PROPERTIES

SEQUENCE-FUNCTION

STRUCTURE-FUNCTION

EVOLUTION

STRUCTURE COMPARISON





Structure-Function


To find protein structure that are related to HSF I used the fold recognition search engine at Ben Gurion University. This search finds pdb files with coordinates which align with the query structure. The following list of pdbs was shown through iterated searching to be closely related to HSF:


PDB hits by PSI-BLAST
PDB code     score  round
 3HTSB       4e-56  1
  3HSF       1e-50  1
  2HTS       1e-46  1
  1HKS       3e-17  1
 3HTSB       8e-40  2
  3HSF       8e-36  2
  2HTS       2e-33  2
  1HKS       3e-29  2
  1ETC         8.1  2
 2STTA         8.1  2
 3HTSB       1e-36  3
  3HSF       8e-34  3
  2HTS       8e-32  3
  1HKS       6e-30  3
 2STTA        0.44  3
  1ETC        0.57  3
 
Fold Recognition Methods summary
 
gonp         gonpm      seqpprf     seqpmprf  prfseq           consensus
3hsf 44.8  3hsf 29.2   3hsf 43.2  3hsf 45.6  3hsf 47.1            3hsf 210.0
1hks 22.5  1hks 23.2   1hks 37.4  1hks 41.2  1hks 40.3            1hks 82.3
2il8  5.3  1etc  6.4   1etc  4.4  1pue  7.5  1etc 10.5            1etc 10.1
1etc  4.9  1pue  4.9   1pue  4.1  1etc  7.1  1pue  3.8           1puee  5.9
1csz  4.2  2il8  4.7   1plf  3.5  1aoy  4.6  1cee  3.5           2il8b  2.9
1tii  3.6  1pyi  3.8   1sdf  3.5  1plf  3.5  1poc  3.3            1aoy  1.9
1alc  3.2  1plf  3.7   1eo0  3.3  1puc  3.5  1aoy  3.3           1plfa  1.8
2phy  3.2  1puc  3.7   1eqt  3.3  1d9a  3.1  1qk9  3.2            1puc  1.4
1fjf  3.2  1ice  3.6   2hfh  3.2  1qk9  3.1  1tbd  3.2           1csza  1.1
1f9m  3.2  1fjf  3.4   2hcc  3.2  1e0b  3.0  2hfh  3.1           1eqta  1.0
1pyi  3.1  1aoy  3.4   1tvx  3.1  2hcc  3.0  1chc  3.0           1pyia  0.9
1faa  3.0  1fcd  3.1   1hum  3.0  1eqt  2.9  1puc  3.0           1fjfk  0.9
1tbd  3.0  1fjg  3.1   1csz  3.0  1mca  2.9  1f3m  2.8            1qk9  0.7
1gbr  3.0  1fia  3.0   1mca  2.9  2phy  2.8  1eqt  2.8           1ceeb  0.7
1puc  3.0  1am3  2.9   1ab2  2.7  2il8  2.8  2drp  2.7            2hfh  0.7
1fjg  3.0  2fxb  2.9   1aoy  2.7  1fcb  2.8  1fjf  2.7            2phy  0.6
1f9m  3.0  1f3m  2.8   1el0  2.5  1mnt  2.7  1fjg  2.7           1tiid  0.6
1pue  3.0  1qdu  2.7   1b2t  2.5  3mon  2.6  1b91  2.7            2hcc  0.6
1dz1  2.9  1pau  2.7   4cpv  2.4  2u2f  2.6  1s9m  2.7           1fjgk  0.6
1eqt  2.8  1lef  2.6   2u2f  2.4  1qkf  2.5  2fxb  2.7            1tbd  0.6

To better understand how the structure of HSF relates to other structures I decided to superimpose the HSF structure and one of the less related structures (1etc) from the list generated by the server at Ben Gurion University. 1etc is the stucture of an ets transcription factor in humans. This structure is also a winged helix-turn-helix domain but has diverged significantly in sequence as shown below:


3HTS:B 14/197 AFVNKLWSMVNDKSNEKFIHWSTSGESIVVPNRERFVQEVLPKYFKH-----SNFASFVR 1ETC:_ 6/337 QLWQFLLELLTDKSCQSFISWTGDGWEFKL----SDPDEVARRWGKRKNKPKMNYEKLSR

3HTS:B 69/252 QLNMYG----WHKVQDVKSGSMLSNNDSRWEFEN 1ETC:_ 62/393 GLRYYYDKNIIHKTAG----------KRYVYRFV

An image of the superposition of these two proteins (HSF in red and 1etc in blue) shows that the recognition helix is the same orientation for both proteins and that both proteins contain the small stabilzing beta sheet. A major difference between the two structures is that the wing of HSF is much larger. This is consistent with its function in stabilizing HSF trimers which ets transcription factors don't form.