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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | rat megalin bodyA | |||||||||
![]() | postprocess map | |||||||||
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![]() | endocytosis receptor / ENDOCYTOSIS | |||||||||
Function / homology | ![]() | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
![]() | Goto S / Tsutsumi A / Lee Y / Hosojima M / Kabasawa H / Komochi K / Yun-san L / Nagatoshi S / Tsumoto K / Nishizawa T ...Goto S / Tsutsumi A / Lee Y / Hosojima M / Kabasawa H / Komochi K / Yun-san L / Nagatoshi S / Tsumoto K / Nishizawa T / Kikkawa M / Saito A | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structures elucidate the multiligand receptor nature of megalin. Authors: Sawako Goto / Akihisa Tsutsumi / Yongchan Lee / Michihiro Hosojima / Hideyuki Kabasawa / Koichi Komochi / Satoru Nagatoishi / Kazuya Takemoto / Kouhei Tsumoto / Tomohiro Nishizawa / Masahide ...Authors: Sawako Goto / Akihisa Tsutsumi / Yongchan Lee / Michihiro Hosojima / Hideyuki Kabasawa / Koichi Komochi / Satoru Nagatoishi / Kazuya Takemoto / Kouhei Tsumoto / Tomohiro Nishizawa / Masahide Kikkawa / Akihiko Saito / ![]() Abstract: Megalin (low-density lipoprotein receptor-related protein 2) is a giant glycoprotein of about 600 kDa, mediating the endocytosis of more than 60 ligands, including those of proteins, peptides, and ...Megalin (low-density lipoprotein receptor-related protein 2) is a giant glycoprotein of about 600 kDa, mediating the endocytosis of more than 60 ligands, including those of proteins, peptides, and drug compounds [S. Goto, M. Hosojima, H. Kabasawa, A. Saito, , 106393 (2023)]. It is expressed predominantly in renal proximal tubule epithelial cells, as well as in the brain, lungs, eyes, inner ear, thyroid gland, and placenta. Megalin is also known to mediate the endocytosis of toxic compounds, particularly those that cause renal and hearing disorders [Y. Hori , , 1783-1791 (2017)]. Genetic megalin deficiency causes Donnai-Barrow syndrome/facio-oculo-acoustico-renal syndrome in humans. However, it is not known how megalin interacts with such a wide variety of ligands and plays pathological roles in various organs. In this study, we elucidated the dimeric architecture of megalin, purified from rat kidneys, using cryoelectron microscopy. The maps revealed the densities of endogenous ligands bound to various regions throughout the dimer, elucidating the multiligand receptor nature of megalin. We also determined the structure of megalin in complex with receptor-associated protein, a molecular chaperone for megalin. The results will facilitate further studies on the pathophysiology of megalin-dependent multiligand endocytic pathways in multiple organs and will also be useful for the development of megalin-targeted drugs for renal and hearing disorders, Alzheimer's disease [B. V. Zlokovic , , 4229-4234 (1996)], and other illnesses. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 3.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.9 KB 22.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.2 KB | Display | ![]() |
Images | ![]() | 187.5 KB | ||
Masks | ![]() | 67 MB | ![]() | |
Filedesc metadata | ![]() | 9.1 KB | ||
Others | ![]() ![]() | 44.1 MB 44.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8jx9MC ![]() 8jutC ![]() 8juuC ![]() 8jx8C ![]() 8jxaC ![]() 8jxbC ![]() 8jxcC ![]() 8jxdC ![]() 8jxeC ![]() 8jxfC ![]() 8jxgC ![]() 8jxhC ![]() 8jxiC ![]() 8jxjC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | postprocess map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.411 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Projections & Slices |
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Density Histograms |
-Half map: halfmap1
File | emd_36693_half_map_1.map | ||||||||||||
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Annotation | halfmap1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: halfmap2
File | emd_36693_half_map_2.map | ||||||||||||
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Annotation | halfmap2 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : rat megalin head domain
Entire | Name: rat megalin head domain |
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Components |
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-Supramolecule #1: rat megalin head domain
Supramolecule | Name: rat megalin head domain / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 1 MDa |
-Macromolecule #1: LDL receptor related protein 2
Macromolecule | Name: LDL receptor related protein 2 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 519.871438 KDa |
Sequence | String: MERGAAAAAW MLLLAIAACL EPVSSQECGS GNFRCDNGYC IPASWRCDGT RDCLDDTDEI GCPPRSCESG LFLCPAEGTC IPSSWVCDE DKDCSDGADE QQNCAGTTCS AQQMTCSNGQ CIPSEYRCDH VSDCPDGSDE RNCHYPTCDQ LTCANGACYN T SQRCDQKV ...String: MERGAAAAAW MLLLAIAACL EPVSSQECGS GNFRCDNGYC IPASWRCDGT RDCLDDTDEI GCPPRSCESG LFLCPAEGTC IPSSWVCDE DKDCSDGADE QQNCAGTTCS AQQMTCSNGQ CIPSEYRCDH VSDCPDGSDE RNCHYPTCDQ LTCANGACYN T SQRCDQKV DCRDSSDEAN CTTLCSQKEF ECGSGECILR AYVCDHDNDC EDNSDERNCN YDTCGGHQFT CSNGQCINQN WV CDGDDDC QDSGDEDGCE SNQSHHRCYP REWACPGSGR CISIDKVCDG VPDCPEGDDE NNVTSGRTCG MGVCSVLNCE YQC HQTPFG GECFCPPGHI INSNDSRTCI DFDDCQIWGI CDQKCENRQG RHQCLCEEGY ILERGQHCKS SDSFSAASVI FSNG RDLLV GDLHGRNFRI LAESKNRGMV MGVDFHYQKH RVFWTDPMQE KVFSTDINGL NTQEILNVSV DTPENLAVDW INNKL YLVE TKVNRIDVVN LEGNQRVTLI TENLGHPRGI ALDPTVGYLF FSDWGSLSGQ PKVERAFMDG SNRKDLVTTK VGWPAG ITL DLVSKRVYWV DSRYDYIETV TYDGIQRKTV ARGGSLVPHP FGISLFEEHV FFTDWTKMAV MKASKFTETN PQVYHQS SL RPHGVTVYHA LRQPNATNPC GSNNGGCAQV CVLSHRTDNG GLGYRCKCEF GFELDDDEHR CVAVKNFLLF SSKTAVRG I PFTLSTQEDV MVPVTGSPSF FVGIDFDAQH STVFYSDLSK DIIYKQKIDG TGKEVITANR LESVECLTFD WISRNLYWT DGGLKSVTVL RLADKSRRQI ISNLNNPRSI VVHPTAGYMF LSDWFRPAKI MRAWSDGSHL MPIVNTSLGW PNGLAIDWSA SRLYWVDAF FDKIEHSTLD GLDRKRLGHV DQMTHPFGLT VFKDNVFITD WRLGAIIRVR KSDGGDMTVI RRGISSVMHV K AYDADLQT GSNYCSQTTH ANGDCSHFCF PVPNFQRVCG CPYGMKLQRD QMTCEGDPAR EPPTQQCGSL SFPCNNGKCV PS FFRCDGV DDCHDNSDEH QCGVFNNTCS PSAFACVRGG QCIPGQWHCD RQNDCLDGSD EQNCPTHATS STCPSTSFTC DNH VCIPKD WVCDTDNDCS DGSDEKNCQA SGTCQPTQFR CPDHRCISPL YVCDGDKDCA DGSDEAGCVL NCTSAQFKCA DGSS CINSR YRCDGVYDCR DNSDEAGCPT RPPGMCHLDE FQCQGDGTCI PNTWECDGHP DCIHGSDEHT GCVPKTCSPT HFLCD NGNC IYKAWICDGD NDCRDMSDEK DCPTQPFHCP STQWQCPGYS TCINLSALCD GVFDCPNGTD ESPLCNQDSC SHFNGG CTH QCMQGPFGAT CLCPLGYQLA NDTKTCEDIN ECDIPGFCSQ HCVNMRGSFR CACDPEYTLE SDGRTCKVTG SENPLLV VA SRDKIIVDNI TAHTHNLYSL VQDVSFVVAL DFDSVTGRVF WSDLLQGKTW SVFQNGTDKR VVHDSGLSVT EMIAVDWI G RNLYWTDYAL ETIEVSKIDG SHRTVLISKN VTKPRGLALD PRMGDNVMFW SDWGHHPRIE RASMDGTMRT VIVQEKIYW PCGLSIDYPN RLIYFMDAYL DYIEFCDYDG HNRRQVIASD LVLHHPHALT LFEDFVYWTD RGTRQVMQAN KWHGGNQSVV MYSVHQPLG ITAIHPSRQP PSRNPCASAS CSHLCLLSAQ APRHYSCACP SGWNLSDDSV NCVRGDQPFL MSVRDNIIFG I SLDPEVKS NDAMVPISGI QHGYDVEFDD SEQFIYWVEN PGEIHRVKTD GSNRTVFAPL SLLGSSLGLA LDWVSRNIYY TT PASRSIE VLTLKGDTRY GKTLIANDGT PLGVGFPVGI AVDPARGKLY WSDHGTDSGV PAKIASANMD GTSLKILFTG NLQ HLEVVT LDIQEQKLYW AVTSRGVIER GNVDGTERMI LVHHLAHPWG LVVYGSFLYY SDEQYEVIER VDKSSGNNKV VLRD NVPYL RGLRVYHRRN AADSSNGCSN NPNACQQICL PVPGGMFSCA CASGFKLSPD GRSCSPYNSF MVVSMLPAVR GFSLE LSDH SEAMVPVAGQ GRNVLHADVD VANGFIYWCD FSSSVRSSNG IRRIKPDGSN FTNVVTYGIG ANGIRGVALD WAAGNL YFT NAFVYETLIE VLRINTTYRR VLLKVSVDMP RHIIVDPKHR YLFWADYGQK PKIERSFLDC TNRTVLVSEG IVTPRGL AM DHDTGYIYWV DDSLDLIARI HLDGGESQVV RYGSRYPTPY GITVFGESII WVDRNLKKVF QASKQPGNTD PPVVIRDK I NLLRDVTIFD EHAQPLSPAE LNNNPCLQSN GGCSHFCFAL PELPTPRCGC AFGTLGNDGK SCATSQEDFL IYSLNNSLR SLHFDPRDHS LPFQVISVAG TAIALDYDRR NNRIFFTQKL NSLRGQISYV SLYSGSSSPT VLLSNIGVTD GIAFDWINRR IYYSDFSNQ TINSMAEDGS NRAVIARVSK PRAIVLDPCR GYMYWTDWGT NAKIERATLG GNFRVPIVNT SLVWPNGLAL D LETDLLYW ADASLQKIER STLTGTNREV VVSTAFHSFG LTVYGQYIYW TDLYTRKIYR ANKYDGSDLV AMTTRLPTQP SG ISTVVKT QRQQCSNPCD QFNGGCSHIC APGPNGAECQ CPHEGNWYLA NDNKYCVVDT GTRCNQLQFT CLNGHCINQD WKC DNDNDC GDGSDELPTV CAFHTCRSTA FTCGNGRCVP YHYRCDYYND CGDNSDEAGC LFRNCNSTTE FTCSNGRCIP LSYV CNGIN NCHDNDTSDE KNCPPHTCPP DFTKCQTTNI CVPRAFLCDG DNDCGDGSDE NPIYCASHTC RSNEFQCLSP QRCIP SYWF CDGEADCADG SDEPDTCGHS VNTCRASQFQ CDNGRCISGN WVCDGDNDCG DMSDEDQRHH CELQNCSSTQ FTCVNS RPP NRRCIPQYWV CDGDADCSDA LDELQNCTMR TCSAGEFSCA NGRCVRQSFR CDRRNDCGDY SDERGCSYPP CHANQFT CQ NGRCIPRFFV CDEDNDCGDG SDEQEHLCHT PEPTCPLHQF RCDNGHCIEM GRVCNHVDDC SDNSDEKGCG INECLDSS I SRCDHNCTDT ITSFYCSCLP GYKLMSDKRS CVDIDECKES PQLCSQKCEN VVGSYICKCA PGYIREPDGK SCRQNSNIE PYLIFSNRYY IRNLTTDGSS YSLILQGLGN VVALDFDRVE KRLYWIDAEK QIIERMFLNK TNRETIINHR LRRAESLAVD WVSRKLYWL DAILDCLFVS DLEGRHRKMI AQHCVDANNT FCFEHPRGIV LHPQRGHVYW ADWGVHAYIG RIGMDGTNKS V IISTKIEW PNAITIDYTN DLLYWADAHL GYIEFSDLEG HHRHTVYDGS LPHPFALTIF EDTVFWTDWN TRTVEKGNKY DG SGRVVLV NTTHKPFDIH VYHPYRQPIM SNPCGTNNGG CSHLCLIKAG GRGFTCACPD DFQTVQLRDR TLCMPMCSST QFL CGNNEK CIPIWWKCDG QKDCSDGSDE PDLCPHRFCR LGQFQCRDGN CTSPQALCNA RQDCADGSDE DRVLCEHHRC ESNE WQCAN KRCIPQSWQC DSVNDCLDNS DEDTSHCASR TCRPGQFKCN NGRCIPQSWK CDVDNDCGDY SDEPIDECTT AAYNC DNHT EFSCKTNYRC IPQWAVCNGF DDCRDNSDEQ GCESVPCHPS GDFRCANHHC IPLRWKCDGT DDCGDNSDEE NCVPRE CSE SEFRCADQQC IPSRWVCDQE NDCGDNSDER DCEMKTCHPE HFQCTSGHCV PKALACDGRA DCLDASDESA CPTRFPN GT YCPAAMFECK NHVCIQSFWI CDGENDCVDG SDEEIHLCFN IPCESPQRFR CDNSRCVYGH QLCNGVDDCG DGSDEKEE H CRKPTHKPCT DTEYKCSNGN CISQHYVCDN VNDCGDLSDE TGCNLGDNRT CAENICEQNC TQLSSGGFIC SCRPGFKPS TLDKNSCQDI NECEEFGICP QSCRNSKGSY ECFCVDGFKS MSTHYGERCA ADGSPPLLLL PENVRIRKYN TSSEKFSEYL EEEEHIQTI DYDWDPEHIG LSVVYYTVLA QGSQFGAIKR AYIPNFESGS NNPIREVDLG LKYLMQPDGL AVDWVGRHIY W SDAKSQRI EVATLDGRYR KWLITTQLDQ PAAIAVNPKL GLMFWTDQGK QPKIESAWMN GEHRSVLVSE NLGWPNGLSI DY LNDDRVY WSDSKEDVIE AIKYDGTDRR LIINEAMKPF SLDIFEDKLY WVAKEKGEVW RQNKFGKENK EKVLVVNPWL TQV RIFHQL RYNQSVSNPC KQVCSHLCLL RPGGYSCACP QGSDFVTGST VQCDAASELP VTMPPPCRCM HGGNCYFDEN ELPK CKCSS GYSGEYCEVG LSRGIPPGTT MAVLLTFVIV IIVGALVLVG LFHYRKTGSL LPTLPKLPSL SSLAKPSENG NGVTF RSGA DVNMDIGVSP FGPETIIDRS MAMNEHFVME VGKQPVIFEN PMYAAKDNTS KVALAVQGPS TGAQVTVPEN VENQNY GRP IDPSEIVPEP KPASPGADEI QGKKWNIFKR KPKQTTNFEN PIYAEMDSEV KDAVAVAPPP SPSLPAKASK RNLTPGY TA TEDTFKDTAN LVKEDSDV UniProtKB: LDL receptor related protein 2 |
-Macromolecule #2: ligand
Macromolecule | Name: ligand / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 472.537 Da |
Sequence | String: (UNK)(UNK)N(UNK)(UNK) |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 2 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #7: 2-acetamido-2-deoxy-alpha-D-galactopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-alpha-D-galactopyranose / type: ligand / ID: 7 / Number of copies: 5 / Formula: A2G |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-A2G: |
-Macromolecule #8: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 8 / Number of copies: 20 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 2.6 mg/mL |
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Buffer | pH: 7.4 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model | Chain - Source name: AlphaFold / Chain - Initial model type: in silico model |
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Output model | ![]() PDB-8jx9: |