Homology based structure predictions
Contents
Homologous
Because we found no homologous structures in Task 2, we extended our list by using HHSearch.
HHSearch found just sequences with an indentity below 40% therefore we will use the 12 proteins shown below for creating a multiple alignment for homologous modeling. We choose sequences to cover the whole protein and we pay specific attention on the transmembrane region.
| PDB-ID | Identity | Description |
| 1s79 | 37% | human La protein |
| 3p73 | 28% | classical MHC class I molecule |
| 1kcg | 22% | NKG2D |
| 1jfm | 14% | MURINE NK CELL LIGAND RAE-1 BETA |
| 1bii | 22% | H-2DD MHC CLASS I |
| 2p24 | 21% | alphabeta TCR |
| 1cd1 | 21% | MHC-like fold with a large hydrophobic binding groove |
| 2wy3 | 29% | HCMV UL16-MICB complex |
| 1lqv | 14% | Endothelial protein C receptor |
| 3jts | 25% | Mamu A*2 |
| 1ow0 | 22% | human FcaRI |
| 1hxm | 18% | Human Vgamma9/Vdelta2 T Cell Receptor |
With these Sequences including the HFE-Gen(Q30201), we did a multible sequence alignment with t-coffee(EXPRESSO). This mutlible sequence alignment is later used as a raw alignment in the Alignment Mode of SwissModel and Modeller. Later on, we will try to fit better models by editing the alignment by keeping functional regions together.
DSSP --EEEEEEEEEEB-SS-SSB--EEEEEETTEEEEEEESSS--EEE--STTS-SSTTTTHHHHHHHHHHHHHHHHH
Q30201 MGPRARPALLLLMLLQTAVLQGRLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDHES--RRVE-PRTPWVSSRISSQMWLQLSQSLKGWDHM
1S79_A --------------------------------------------------------------------GRW-IL-KNDVKNRSVYIKGFPTDATLDDIKE
3P73_A -----------------------EFGSHSLRYFLTGMTDPGPGMPRFVIVGYVDDKIFGTYNSKS--RTAQ-PIVEML-PQEDQEHWDTQTQKAQGGERD
1KCG_C -------------------------DAHSLWYNFTIIHLPRHGQQWCEVQSQVDQKNFLSYDCGS--DKVLSMGHL-EEQLYATDAWGKQLEMLREVGQR
1JFM_A -------------------------DAHSLRCNLTIKDPTPADPLWYEAKCFVGEILILHLSNIN--KTMT-SG-DPGETANATEVKKCLTQPLKNLCQK
1BII_A -MGAMAPRTLLLLLAAALGPTQTRAGSHSLRYFVTAVSRPGFGEPRYMEVGYVDNTEFVRFDSDAENPRYE-PRARWIE-QEGPEYWERETRRAKGNEQS
2P24_A ----------------------------------------------------------------------------M----AIMAPRTLVLLLSGALALT
1CD1_A -----------------------QQKNYTFRCLQMSSFANR-SWSRTDSVVWLGDLQTHRWSNDS--ATIS-FTKPWSQGKLSNQQWEKLQHMFQVYRVS
2WY3_A ------------------------MEPHSLRYNLMVLSQDESVQSGFLAEGHLDGQPFLRYDRQK--RRAK-PQGQWAEDVLGAETWDTETEDLTENGQD
1LQV_A -------------------SQDASDGLQRLHMLQISYFR-DPYHVWYQGNASLGGHLTHVLEGPDTNTTII-QLQPL----QEPESWARTQSGLQSYLLQ
3JTS_A -------------------------GSHSMRYFYTSMSRPGRWEPRFIAVGYVDDTQFVRFDSDAASQRME-PRAPWVE-QEGPEYWDRETRNMKAETQN
1OW0_A ----------------------------------------------------------------------------------------------------
1HXM_A -------------------------------------------------------------------------------------AIELVPEHQTVPVSI
DSSP HHHHHHHHTTT-SSS--E--------EEEEEE-EEE-TTS-E-EEE-E------------EEEETTEE----------------EEEEEGGGTEEEES--
Q30201 FTVDFWTIMENHN-HSKE--------SHTLQV-ILGCEMQED-NST-E------------GYWKYGYD----------------GQDHLEFCPDTLDW--
1S79_A WLEDKGQV-LNIQMRRTL--------HKAFKG-SIFVVFDSI-ESA-KKFVETPGQKYKETDLLILFKDDYFAKKNEERKQNKVE---------------
3P73_A FDWNLNRLPERYN-KSKG--------SHTMQM-MFGCDILED-GSI-R------------GYDQYAFD----------------GRDFLAFDMDTMTF--
1KCG_C LRLELADT---------ELEDFTPSGPLTLQV-RMSCECEAD-GYI-R------------GSWQFSFD----------------GRKFLLFDSNNRKW--
1JFM_A LRNKVSNT-KVDTHKTNG--------YPHLQV-TMIYPQSQG-RTP-S------------ATWEFNIS----------------DSYFFTFYTENMSW--
1BII_A FRVDLRTALRYYNQSAGG--------SHTLQW-MAGCDVESD-GRLLR------------GYWQFAYD----------------GCDYIALNEDLKTW--
2P24_A QTWAGSHSRGEDD--IEA--------DHVGSYGIVVYQSP----GD-I------------GQYTFEFD----------------GDELFYVDLDKKET--
1CD1_A FTRDIQELVKMMSPKEDY--------PIEIQL-SAGCEMYPG-NAS-E------------SFLHVAFQ----------------GKYVVRFWG--TSWQT
2WY3_A LRRTLTHI----KDQKGG--------LHSLQE-IRVCEIHED-SST-R------------GSRHFYYN----------------GELFLSQNLETQES--
1LQV_A FHGLVRLVHQERT--LAF--------PLTIRC-FLGCELPPEGSRA-H------------VFFEVAVN----------------GSSFVSFRPERALW--
3JTS_A APVNLRNLRGYYNQSEAG--------SHTIQR-MYGCDLGPD-GRLLR------------GYHQSAYD----------------GKDYIALNEDLRSW--
1OW0_A -----ACHPRLSLHRPAL--------EDLLLG-SEANLTCTL-TGLRD------------ASGVTFTW----------------TPSSGKSAV--QGPPE
1HXM_A GVPATLRCSMKGEAIGNY--------YINWYR-KTQGNTMTF-IYRE-------------KDIYGPGF----------------KDNFQGDIDIAKNL--
DSSP SGG-G----HHH-HHHHHSSTHHH--HHHHHHHHTHHHHHHHHHHHHHTTTSS--B--EEEEEEEE-SS-----E-EEEEEEEEEBSS--EEEEEETTEE
Q30201 RAA-E----PRA-WPTKLEWERHK--IRARQNRAYLERDCPAQLQQLLELGRGVLDQQVPPLVKVTHHVT----S-SVTTLRCRALNYYPQNITMKWLKD
1S79_A ----------------------------------------------------------------------------------------------------
3P73_A TAA-D----PVA-EITKRRWETEG--TYAERWKHELGTVCVQNLRRYLEHGKAALKRRVQPEVRVWGKEA----D-GILTLSCHAHGFYPRPITISWMKD
1KCG_C TVV-H----AGA-RRMKEKWEKDS--GLTTFFKMVSMRDCKSWLRDFLMHRKKRLE--------------------------------------------
1JFM_A RSA-N----DES-GVIMNKWKDDG--EFVKQLKFLI-HECSQKMDEFLKQSKEK----------------------------------------------
1BII_A TAA-D----MAA-QITRRKWEQA---GAAERDRAYLEGECVEWLRRYLKNGNATLLRTDPPKAHVTHHRR----PEGDVTLRCWALGFYPADITLTWQLN
2P24_A IWM-------------LPEFAQLR--SFDPQGGLQNIATGKHNLGVLTKRSNSTPATNEAPQATVFPKSP--VLLGQPNTLICFVDNIFPPVINITWLRN
1CD1_A VPGAP----SWL-DLPIKVLNADQ--GTSATVQMLLNDTCPLFVRGLLEAGKSDLEKQEKPVAWLSSVP---SSAHGHRQLVCHVSGFYPKPVWVMWMRG
2WY3_A TVP-QSSRAQTLAMNVTNFW-KEDAMKTKTHYRAMQ-ADCLQKLQRYLKSGVAIRRTVPPMVNVTCSEVS----EGNITVTCRASSFYPRNITLTWRQDG
1LQV_A QAD-TQVTSGVV-TFTLQQLNAYN--RTRYELREFLEDTCVQYVQKHISAENTKGSQTSRSYTS------------------------------------
3JTS_A TAA-D----MAA-QNTQRKWEAA---GEAEQHRTYLEGECLEWLRRYLENGKETLQRADPPKTHVTHHPV----SDQEATLRCWALGFYPAEITLTWQRD
1OW0_A R--DL----CGC-YSVSSVLPGCA--EPWNHGKTFTCTAAYPESKTPLTATLSKSGNTFRPEVHLLPPPSEELALNELVTLTCLARGFSPKDVLVRWLQG
1HXM_A AVL-K----ILA-PSERDEGSYYC--ACDTLGMGGEYTDKLIFGKGTRVTVEPRSQPHTKPSVFVMKNG---------TNVACLVKEFYPKDIRINLVSS
DSSP --GGGS---EEEE-TTS-E----EEEEEEEE-TTGGGGEE---EEEE-TTSSS-EEE-E-
Q30201 K-QPMDAKEFEPKDVLPNG----DGTYQGWITLAVPPGEE---QRYTCQVEHPGLDQ-PLIVIWEPSPSGTLVIGVISGIAVFVVILFIGILFIILRKRQ
1S79_A ----------------------------------------------------------------------------------------------------
3P73_A --GMVRDQETRWGGIVPNS----DGTYHASAAIDVLPEDG---DKYWCRVEHASLPQ-PGLFSWEPQ---------------------------------
1KCG_C ----------------------------------------------------------------------------------------------------
1JFM_A ----------------------------------------------------------------------------------------------------
1BII_A --GEELTQEMELVETRPAG----DGTFQKWASVVVPLGKE---QKYTCHVEHEGLPE-PLTLRWGKEEPPSSTKTNTVIIAVPVVLGAVVILGAVMAFVM
2P24_A --SKSVADGVYETSFFVNR----DYSFHKLSYLTFIPSDD---DIYDCKVEHWGLEE-PVLKHWEPEIPAPMSELTETSGSRLEVLFQ------------
1CD1_A --DQ-EQQGTHRGDFLPNA----DETWYLQATLDVEAGEE---AGLACRVKHSSLGG-QDIILYWDARQAPVGLIVFIVLIMLVVVGAVVYYIWRRRSAY
2WY3_A --VSLSHNTQQWGDVLPDG----NGTYQTWVATRIRQGEE---QRFTCYMEHSGNHG-THPVPSGKVLVLQSQRTDFPYVSAAMPCFVIIIILCVPCCKK
1LQV_A ----------------------------------------------------------------------------------------------------
3JTS_A --GEDQTQDTELVETRPAG----DGTFQKWAAVVVPSGKE---QRYTCHVQHEGLRE-PLTLRWEP----------------------------------
1OW0_A SQEL-PREKYLTW-ASRQEPSQGTTTFAVTSILRVAAEDWKKGDTFSCMVGHEALPLAFTQKTIDRLAGK------------------------------
1HXM_A -----KKITEFDPAIVISP----SGKYNAVKLGKYE--DS---NSVTCSVQHDNK---TVHSTDFEVKTDSTDHVKPKETENTKQPSKS-----------
DSSP
Q30201 GSRGAMGHYVLAERE----------------
1S79_A -------------------------------
3P73_A -------------------------------
1KCG_C -------------------------------
1JFM_A -------------------------------
1BII_A KRRRNTGGKGGDYALAPGSQSSDMSLPDCKV
2P24_A -------------------------------
1CD1_A QDIR---------------------------
2WY3_A KTSAAEGP-----------------------
1LQV_A -------------------------------
3JTS_A -------------------------------
1OW0_A -------------------------------
1HXM_A -------------------------------
Based on the secondary structure for the HFE-Gen assigned by DSSP from the PDB structure (1a6z) the multible sequence alignmet conserves most parts of the secondary structure.
ITasser
Predicted Secondary Structure by I-Tasser
Sequence: MGPRARPALLLLMLLQTAVLQGRLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDHESRRVEPRTPWVSSRISSQMWLQLSQSLKGWDHMFTVDF Predicted: CCCCHHHHHHHHHHHHHHHHHHHHCCCCCCCSSSSSCCCCCCCCCCSSSSSSSCCCSSSSCCCCCCCCCCCCCCCCCCCCCHHHHHHHHHHHHHHHHHHHHH Conf-Score: 985028899999999899875122045421036641367999985269985643743686068998778788540145583478888887676654315558 Sequence: WTIMENHNHSKESHTLQVILGCEMQEDNSTEGYWKYGYDGQDHLEFCPDTLDWRAAEPRAWPTKLEWERHKIRARQNRAYLERDCPAQLQQLLELGRGVLDQ Predicted: HHHHHHHCCCCCCSSSSSSSCCCCCCCCCCCCCCCCCCCCCCSSSSCCCHHHCHHHHHHHHHHHHHHHHCCCHHHHHHHHHCCCCHHHHHHHHHCCHHHHHC Conf-Score: 888755315777644463525565898763541000558873365263022202455666677878887004598888767064299999999747666642 Sequence: QVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWEPSPSGTLV Predicted: CCCCCCCCCCCCCCCHHHHCHHHHCCCCCCSSSSSSSCCCCCCCCCCSSSSCCCCCCCCCCCSSSSSCCCCCCCCSSSSCCCCCCCCCSSSSCCCCCCCCCC Conf-Score: 599877567699854442101541541332479864358754456553541024888652112699807986310267512589998726840688766531 Sequence: IGVISGIAVFVVILFIGILFIILRKRQGSRGAMGHYVLAERE Prediction: CCCCCCHHHHHHHCCHHHHHHHHHCCCCCCCCCCCCCHCCCC Conf-Score: 010211112222100246665443013678898651020169
Secondary structure elements are shown as H for Alpha helix,S for Beta sheet & C for Coil
Predicted Solvent Accessibility by I-Tasser
Sequence: MGPRARPALLLLMLLQTAVLQGRLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDHESRRVEPRTPWVSSRISSQMWLQLSQSLKGWDHMFTVDF Prediction: 723312000000000101112222011200120120023333331200000102322003123724434241311436413610352044144313323230 Sequence: WTIMENHNHSKESHTLQVILGCEMQEDNSTEGYWKYGYDGQDHLEFCPDTLDWRAAEPRAWPTKLEWERHKIRARQNRAYLERDCPAQLQQLLELGRGVLDQ Prediction: 220132133351310001010021136231211333023032003016303403102321432433044143404422010333005103400630351154 Sequence: QVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWEPSPSGTLV Prediction: 342353313321443300000100101014010203346564435434135233334221320000000347533120214264144202020214542200 Sequence: IGVISGIAVFVVILFIGILFIILRKRQGSRGAMGHYVLAERE Prediction: 000001100000011100000001334446443132333438
Values range from 0 (buried residue) to 9 (highly exposed residue)
I-Tasser predicted five Models with a C-Score from -0.557 to -3.298. They are ranked from one to five as seen below.
Model1 has a TM-Score of about 0.64 and a RMSD of 7.7Å. For the prediction, I-Tasser used 1a6zA, 1s7qA, 1i4fA, 1de4A, 2vabA and 2bckA as templates. The templates have an identity of about 40% except for the self hit 1a6z. Because of the self hit, we run I-Tasser a second time with the constrain to exclude all templates with a sequence identity > 80%.
I-Tasser using templates with a sequence identity below 80% to avoid self hits.
SwissModel
SwissProt is a server based tool provided by the SIB. It combines tools like PSI-PRED and DISOPRED for secondary structure and disordered region prediction.
The model created by SwissModel is based on a self hit, but we had no chance to exclude the protein itself from the prediction. Therefore we also run SwissModel in Alignment-Mode.(TODO)
Automated Mode
Model information:
Modelled residue range: 26 to 297
Based on template: 1a6zC (2.60 Å)
Sequence Identity [%]: 100
Evalue: 7.66e-163
Quality information:
QMEAN Z-Score: -1.035
Even though the model is based on a self hit, the Z-Score is about -1, which means that the model is one standard deviation from the mean. The model is not quite unlikely but also not the most probable one.
Alignment Mode
Modeller
References
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