Sequence alignment of CTLDs from C elegans

Sequence alignment for (potential) sugar-binding CTLDs

Sequence alignments for CTLD evolutionary groups: 1 2 3 4 5 6 7 8

Analysis of potential Ca²⁺- and sugar-binding sites

Identification of CTLDs is based on similarity in the basic fold of these domains. None of the C. elegans CTLDs is particularly similar to any mammalian CTLDs, so overall sequence comparison is not a useful route to predicting functions of the C. elegans proteins. A more sensitive approach is to search for conservation of amino acid side chains that form ligand-binding sites in CTLDs with known binding properties. Amongst the CTLDs, the best characterized is the CRD of mannose-binding protein. In this case, the key residues are those that surround one of the two Ca²⁺-binding sites, Ca²⁺ site 2, since this portion of the protein forms the carbohydrate-binding site. Five acid and amide side chains form this site. Multiple sequence alignments have been used to identify a subset of CTLDs in C. elegans in which some or all of these residues are conserved. The predicted core monosaccharide-binding activity of some of these CTLDs is based on the arrangement of acid and amide groups around Ca²⁺ site 2. In some cases, the pattern has not been seen in a sugar-binding CTLD, so the possibility of a novel sugar-binding activity must be entertained. The structural subgroups refer to the domain organization of the protein containing the CTLD.

Regions of secondary structure are indicated at the top of the alignments: a-helices and b-strands are denoted by H and S respectively. Residues indicated with 1, 2 or 3 correspond to ligands for Ca²⁺ ions. Residues highlighted in green are ligands for Ca²⁺ion 1. Residues highlighted in violet are ligands for Ca²⁺ ion 2. Cysteine residues are highlighted in yellow. Residues highlighted in blue are conserved residues in the core of the C-type CRD fold. The predicted sugar-binding specificity is indicated at the right-hand side of the alignment.

Abbreviations: RHL-1 - rat hepatic lectin 1; CHL - chicken hepatic lectin; MBP-A - rat serum mannose binding protein; MMR CRD-4 - human macrophage mannose receptor carbohydrate recognition domain 4; Gal - galactose; GlcNAc - N-acetylglucosamine; Man - mannose.

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STRUCTURE S1-------- H1--------- H2--------- S2---- L1------

MOTIF C F A C A A O E HA FAGA 1 1

AGGRECAN VCEEGWNKYQ------GHCYRHFPDRET-------WVDAERRCRE-QQSHLSSIVTPEEQEFVN-----------------NNAQDYQWIGLNDRTIEGD----------

RHL-1 CCPINWVEYE------GSCYWFSSSVKP-------WTEADKYCQL-ENAHLVVVTSWEEQRFVQ----------------QHMGPLNTWIGLTDQNGP------------

CHL AQSRQWEYYE------GRCYYFSLSRMS-------WHKAKAECEE-MHSHLIIIDSYAKQNFVM----------------FRTRNERFWIGLTDENQEGE----------

MBP-A --LHAFSMGK---KSGKKFFVTNHERMP-------FSKVKALCSE-LRGTVAIPRNAEENKAIQ-----------------EVAKTSAFLGITDEVTEGQ----------

E-SELECTIN ----LVLLIK---ESGAWSYNTSTEAMT-------YDEASAYCQQ-RYTHLVAIQNKEEIEYLNS--------------ILSYSPSYYWIGIRKVNNV------------

MMR-CRD-4 KCPEDWGASS----RTSLCFKLYAKGKH---EKKTWFESRDFCRA-LGGDLASINNKEEQQTIWR--------------LITSYHKLFWIGLTYGSPSEG----------

SUBGROUP A8

F47C12.4 GKVVKYKFDVPPGWLDFRRLNGQVVLHWLSEEKLKFTDAAKACEA-KGAHLAGINSLKEAEQLG-----------NHVVGAKLNNEQFWLGAQRKTECLENNDWKAP

T04A8.3 -GTNGFREYKRVKTGQLWCHKYVHDMSMN------NDDAEKKCND-MGAHLSSFTTYEELKLLD---------EMILEVYPNDNNIAVWLGAKRREECGDLSKNFT-GGY

SUBGROUP D4 (SECOND CTLD)

F10F2.7 KCPEGFSEFPRVTSGQRWCHKYVHGAPLP------YDDAEKKCAE-MGAHLSGFTTQEEFKFLN---------ELVNKEYPNKNDIEVWLGAQRKMSCPDAGKNFN-GGF

F10F2.6 ACSDGFSSYYRAALGIQWCHKLVSNKEVV------YSEAEKECDS-LGAHVSGFSDQTELDFMH--------NMTMKSSLGRHHYSNVYIGARRRPECIKLGVSDQIPGF

F10F2.8 PCPAGFLQYDRTELGIRWCHKLYSELETT------YDDAEKECLS-LGAHVSGFSDLKEKDFMH--------DMIMASPIKNKTFNRVWIGAQRRPECNTLGVEGKTGGF

SUBGROUP D1 (SECOND CTLD)

T03F1.10 HCPSGYTWFE----TTDFCYKTTVQFT-------NFNDARSACQA-DGGDLASIHSIAENAFLV------GLSKAGITNKDKDWNDDVWIGLVYQNSK------------

B0218.8 HCPSGYTWFE----LTDFCYKNTVQYT-------NFNDARSACQA-DGGDLASIHSLAENTFLV------GFSKAGCTNKDKDWTGDVFIGLVFQNSK------------

B0218.6 HCPSGYTWYD----ETDFCYKNTVRFT-------SFNDARSSCQA-DGGDLASIHSANENQFLV------DLSKAGITNKDKSHSDDVFIGLVYQNSK------------

SUBGROUPS A1/2/3

W10G11.12 KCPDTWKWFK--RSRGGWCMKVFAAIGT-------QADAEAKCKA-EGAVVAGVQNTEEIKWMS----------ATLQSLQTNPVGTLWVGAKRTKPCISSGLTKQ----

W09G10.5 NCPTGWTWFL--RSRGGWCMKVFTEALN-------QPSAEAKCKA-AEAVLAGIQNKEEVAWMS-----------------KELTGTMWIGTKRTPPCMNSGVTKQ----

C31G12.2 PCPTGWEEFE--RPSGTWCIKMYAALGD-------RANAISACAA-EEAVLSGVQNQAELDYMI--------TAFNAVDTIMAMDTTFWIGGERTSACLTSGLTAT----

F16H6.2 PCPTGWEEFE--RPSGTWCIKTFAIVGS-------WQDGQNGCAT-HGAVLSGVQNQAELDFMC----------------DSAVEGAFWVGGQRTAACPGPGLTAT----

W04H10.4 YDSHANKRYT--VVPIQKCIETFFKLFVGLYLQGNRNEASARCAT-EGAVLSGVQNKAELNAMINGILTNRFYGRFSGQFTRLGNGYFWVGAMRKTSCLMSQLTAT----

F49H6.1 PCPTDWEEFV--RPSGTWCIRVFMGIGD-------QPTAAGLCGG-EGAVLTSIQSQEELDFMR-----------SSYNTVVGTLGFFWIGGQRTGACISSGLTAT----

ZK39.5 TCETGWSVQG-LRASGFWCVKVFLGTYT-------QPQAQAQCEA-VGATLSGIQSANDAQVFQ----------SLGLAALGGQSGSFWIGARRRAACQTQRITAD----

ZK39.6 TCDTGWQLFS--RPSGEWCVKAFAGAYT-------QPLAQAQCIS-AGAILSGVQGHNEAAAFS----------NLGLTSLGNQSGSFWIGAHRITTCMTQIITAQ----

ZK39.7 GCDSGWKRFN--RPSGAWCIRIYRGTHS-------QADAENRCRQNVGATLSGVQNQVEINFIT----------KSALDLISEASGSIWIGGRRTQACRNSALSTS----

T26E3.1 GCDAGWRRFN--RPNGGWCVRVFGARMT-------QADAQIQCQS-YGATLSSLQNMEEALQIN----------NMALSVIKANTGSVWIGAKRTTACLKQWLWTNG---

SUBGROUP D3 (SECOND CTLD)

C14A6.1 SCDQGWTYFS----PTDFCYRVYHGEK--------FNDAEASCVL-LGGHLASIHSLAENTFVN--------NIASCGIKEGKYEHLAWIGMHKVGQD------------

W04E12.6 SCDQGWTYFS----PTDFCYRVYHGEK--------FNDAEASCVL-LGGHLASIHSLTENTFVN--------NIASCGIKEGKYEHLAWIGMRKVGQD------------

W04E12.8 SCDQGWTYFA----PTDFCYRVYHNAK--------WEDAEAACVL-LGAHLTSVHSETENTFVA--------NLASCGIKEGNPKDLAWIGMHKVGQD------------

STRUCTURE L2---- L3----- L4-------- S3-- S4--- S5-----

MOTIF F H G H W 2P2_*+ 3 21CA3H G W22+3C H C

AGGRECAN -------------FRWSDGHP--------MQFENWRP-NQPDNFFAA----GEDCVVMI---------------WHEKGEWNDVPCNY--------------HLPFTCKK

RHL-1 -------------WKWVDGTD------YETGFKNWRP-GQPDDWYGHGLGGGEDCAHFT-----------------TDGHWNDDVCRR--------------PYRWVCET

CHL -------------WQWVDGTD------TRSSFTFWKE-GEPNNRGFN-----EDCAHVW-----------------TSGQWNDVYCTY--------------ECYYVCEK

MBP-A -------------FMYVTGGR--------LTYSNWKK-DEPNDHGSG-----EDCVTIV-----------------DNGLWNDISCQA--------------SHTYVCEF

E-SELECTIN -------------WVWVGTQK-----PLTEEAKNWAP-GEPNNRQKD-----EDCVEIY------------IKREKDVGMWNDERCSK--------------KKLYLCYT

MMR-CRD-4 -------------FTWSDGSP--------VSYENWAY-GEPNNYQNV-----EYCGELK---------------GDPTMSWNDINCEH--------------LNNWICQI

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SUBGROUP A8

F47C12.4 -------CTRGKIFEWNNNVA---TDFREEWWKKNNNNHSPNPSGTG-----QRCLSFA-------FGDLYWSEKGDKGFLDDIECHNE--------------LRYFCSK Sugar?

T04A8.3 SKDIHDPCARSRVFEWQNGVAQNPPIFVGDGFDYWAEKYEPNHSTDS-----ERCLVQM----SGSMSVWWGDNKPRNMQINDIYCNYE--------------FKFLCGK GlcNAc

SUBGROUP D4 (SECOND CTLD)

F10F2.7 STNEFDNCARSRVFEWRNGVAKNPPDFIGSGYDNWAELDEPNHLSDK-----ERCVVMMHGKITKYWGYSSKYHDRRDMQINDIFCDWH--------------FEYFCGL GlcNAc

F10F2.6 DTDDSKPCARFRVFSWLHGVA----LNPPDFASNWMTDKEPNFVGNE-----EQCIVVMT-------GTPPQWRYNGDKKINDIPCTDR--------------YPFFCGK Man

F10F2.8 DTDDSKPCARSRVFYWLHGVA----LNPPDFIEHWADPNEPNFLGDK-----EKCVVVMT------GSEWTHWKFGINKKINDVSCGRR--------------YPFFCGK Man

SUBGROUP D1 (SECOND CTLD)

T03F1.10 -------------WQWTDGSV--------VNYVNWGD-GEPNNMNK------EWWTALV--------ADPHEGKNSEGTRWNNVPQDDQ--------------RAFLCKI Man

B0218.8 -------------WQWTDGSV--------VDYVNWGD-GEPNNMNK------EWWTSLV--------ADPHQGKYSEASRWNNVPQDDQ--------------RAFLCKI Man

B0218.6 -------------WQWTDGSA--------VNFLNWGD-GEPNNMDK------EWWTSLV--------ADPHEDKNTENTRWNNVAQIDM--------------RAFICKK Man

SUBGROUPS A1/2/3

W10G11.12 -------CSAITSFYWSDQSA-----VGVQGFF-WRA-GEPNNALGG-----QGCAQVY----------------STTNDMDDVGCGST-------------NQGYICGK Sugar?

W09G10.5 -------CSQITSYYWTDGST-----VGVQGFY-WNS-GEPNNQGG------QGCAKLI----------------TSSSVLDDVACTTE------------LTNGYVCGK Sugar?

C31G12.2 --------TALTSFEWTDGST-----TGTDGWI-WRS-GEPNNAGGL-----EICATVE----------------ITYVSLADQRCDRAD------------FNGYACGK

F16H6.2 -------CTALTSFEWTDGST-----TGTDGWI-WRP-IEPNNA----------------------------------------ACTRSD------------FDGYVCGK

W04H10.4 -------CTALNSFEWTDGST-----TGTDGFI-WKA-GDPNNYQYN--LYDEPCVAAD------------------VNLMEDIACTRT------------DVTGYACGK Sugar?

F49H6.1 -------CTALNSFSWTDGSA-----TGTAGFV-WNT-GQPDNGGAM---LNEPCVTVN-----------------YLGVLSDDACDRYD------------GFGYACGK Sugar?

ZK39.5 -------CTAQNSFEWTDDTV-----TGTDGFV-WND-KQPDNSDLN-----SGCAVLL----ASGPPVQWGNGMWAGAKLDDHVCDFVDKTPANPRR---VYRGYICGK Sugar?

ZK39.6 -------CTPTNSFSWTDNSA-----TRTDGFV-WET-QQPDNSDFN-----SSCAVIL----AANVPVMAAQRWWSPSKLDDHVCGYVDEDVSNPRR----VRGYICGK Sugar?

ZK39.7 -------CGSLNSFQWTDGST-----TGTAGLV-WNT-NQPDNKDSR----SQQCLVLL----ASRASSIQDKWTWYANRMDDVQCAASGGESAARALRAYAYMNFICNP Sugar?

T26E3.1 -------CGRQNSFAWTDGSA-----TGVAGFV-WDN-LQPDNDELK-----QPCAVML----AARAAVTWGGKFWQPAMLDDNNCMFDLEGKHPRS-----VYGYVCGK Sugar?

SUBGROUP D3 (SECOND CTLD)

C14A6.1 -------------WVWTDGTP--------SDYFNWAP-KQPDNPKK------EFCVQTA----------PDLSHDKWYENWNNLECNEV-------------MRAYICKK Gal

W04E12.6 -------------WVWTDGTP--------SDYFNWAP-KQPDNPKK------ELCVQTA----------PDLSHDKWYENWNNLECNEV-------------MRAYICKK Gal

W04E12.8 -------------WVWTDGTP--------SNYINWAP-KQPDNPGK------ENCVETA----------PDLSHDKWYENWNNEACSTE-------------MRAYICKK Gal

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This page last updated:	Wednesday, 01 January 2014	Animal lectins home
Contact information:	This site is supported by:
Kurt Drickamer Division of Molecular Biosciences Faculty of Natural Sciences Imperial College London Email: k.drickamer@imperial.ac.uk