+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-12942 | |||||||||||||||
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Title | (h-alpha2M)4 transient II state | |||||||||||||||
Map data | (h-alpha2M)4 transient II state | |||||||||||||||
Sample |
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Biological species | Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 12.0 Å | |||||||||||||||
Authors | Luque D / Goulas T / Mata CP / Mendes SR / Gomis-Ruth FX / Caston JR | |||||||||||||||
Funding support | Spain, 4 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 Title: Cryo-EM structures show the mechanistic basis of pan-peptidase inhibition by human α-macroglobulin. Authors: Daniel Luque / Theodoros Goulas / Carlos P Mata / Soraia R Mendes / F Xavier Gomis-Rüth / José R Castón / Abstract: Human α2-macroglobulin (hα2M) is a multidomain protein with a plethora of essential functions, including transport of signaling molecules and endopeptidase inhibition in innate immunity. Here, we ...Human α2-macroglobulin (hα2M) is a multidomain protein with a plethora of essential functions, including transport of signaling molecules and endopeptidase inhibition in innate immunity. Here, we dissected the molecular mechanism of the inhibitory function of the ∼720-kDa hα2M tetramer through eight cryo–electron microscopy (cryo-EM) structures of complexes from human plasma. In the native complex, the hα2M subunits are organized in two flexible modules in expanded conformation, which enclose a highly porous cavity in which the proteolytic activity of circulating plasma proteins is tested. Cleavage of bait regions exposed inside the cavity triggers rearrangement to a compact conformation, which closes openings and entraps the prey proteinase. After the expanded-to-compact transition, which occurs independently in the four subunits, the reactive thioester bond triggers covalent linking of the proteinase, and the receptor-binding domain is exposed on the tetramer surface for receptor-mediated clearance from circulation. These results depict the molecular mechanism of a unique suicidal inhibitory trap. | |||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_12942.map.gz | 12.1 MB | EMDB map data format | |
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Header (meta data) | emd-12942-v30.xml emd-12942.xml | 13.6 KB 13.6 KB | Display Display | EMDB header |
Images | emd_12942.png | 168.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-12942 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-12942 | HTTPS FTP |
-Validation report
Summary document | emd_12942_validation.pdf.gz | 325.7 KB | Display | EMDB validaton report |
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Full document | emd_12942_full_validation.pdf.gz | 325.3 KB | Display | |
Data in XML | emd_12942_validation.xml.gz | 6.7 KB | Display | |
Data in CIF | emd_12942_validation.cif.gz | 7.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12942 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12942 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_12942.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | (h-alpha2M)4 transient II state | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.047 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : Human alpha-2-macroglobulin transient II state
Entire | Name: Human alpha-2-macroglobulin transient II state |
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Components |
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-Supramolecule #1: Human alpha-2-macroglobulin transient II state
Supramolecule | Name: Human alpha-2-macroglobulin transient II state / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) / Organ: Blood plasma |
Molecular weight | Theoretical: 700 KDa |
-Macromolecule #1: Alpha-2-macroglobulin
Macromolecule | Name: Alpha-2-macroglobulin / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Sequence | String: MGKNKLLHPS LVLLLLVLLP TDASVSGKPQ YMVLVPSLLH TETTEKGCVL LSYLNETVTV SASLESVRG NRSLFTDLEA ENDVLHCVAF AVPKSSSNEE VMFLTVQVKG PTQEFKKRTT V MVKNEDSL VFVQTDKSIY KPGQTVKFRV VSMDENFHPL NELIPLVYIQ ...String: MGKNKLLHPS LVLLLLVLLP TDASVSGKPQ YMVLVPSLLH TETTEKGCVL LSYLNETVTV SASLESVRG NRSLFTDLEA ENDVLHCVAF AVPKSSSNEE VMFLTVQVKG PTQEFKKRTT V MVKNEDSL VFVQTDKSIY KPGQTVKFRV VSMDENFHPL NELIPLVYIQ DPKGNRIAQW QS FQLEGGL KQFSFPLSSE PFQGSYKVVV QKKSGGRTEH PFTVEEFVLP KFEVQVTVPK IIT ILEEEM NVSVCGLYTY GKPVPGHVTV SICRKYSDAS DCHGEDSQAF CEKFSGQLNS HGCF YQQVK TKVFQLKRKE YEMKLHTEAQ IQEEGTVVEL TGRQSSEITR TITKLSFVKV DSHFR QGIP FFGQVRLVDG KGVPIPNKVI FIRGNEANYY SNATTDEHGL VQFSINTTNV MGTSLT VRV NYKDRSPCYG YQWVSEEHEE AHHTAYLVFS PSKSFVHLEP MSHELPCGHT QTVQAHY IL NGGTLLGLKK LSFYYLIMAK GGIVRTGTHG LLVKQEDMKG HFSISIPVKS DIAPVARL L IYAVLPTGDV IGDSAKYDVE NCLANKVDLS FSPSQSLPAS HAHLRVTAAP QSVCALRAV DQSVLLMKPD AELSASSVYN LLPEKDLTGF PGPLNDQDNE DCINRHNVYI NGITYTPVSS TNEKDMYSF LEDMGLKAFT NSKIRKPKMC PQLQQYEMHG PEGLRVGFYE SDVMGRGHAR L VHVEEPHT ETVRKYFPET WIWDLVVVNS AGVAEVGVTV PDTITEWKAG AFCLSEDAGL GI SSTASLR AFQPFFVELT MPYSVIRGEA FTLKATVLNY LPKCIRVSVQ LEASPAFLAV PVE KEQAPH CICANGRQTV SWAVTPKSLG NVNFTVSAEA LESQELCGTE VPSVPEHGRK DTVI KPLLV EPEGLEKETT FNSLLCPSGG EVSEELSLKL PPNVVEESAR ASVSVLGDIL GSAMQ NTQN LLQMPYGCGE QNMVLFAPNI YVLDYLNETQ QLTPEIKSKA IGYLNTGYQR QLNYKH YDG SYSTFGERYG RNQGNTWLTA FVLKTFAQAR AYIFIDEAHI TQALIWLSQR QKDNGCF RS SGSLLNNAIK GGVEDEVTLS AYITIALLEI PLTVTHPVVR NALFCLESAW KTAQEGDH G SHVYTKALLA YAFALAGNQD KRKEVLKSLN EEAVKKDNSV HWERPQKPKA PVGHFYEPQ APSAEVEMTS YVLLAYLTAQ PAPTSEDLTS ATNIVKWITK QQNAQGGFSS TQDTVVALHA LSKYGAATF TRTGKAAQVT IQSSGTFSSK FQVDNNNRLL LQQVSLPELP GEYSMKVTGE G CVYLQTSL KYNILPEKEE FPFALGVQTL PQTCDEPKAH TSFQISLSVS YTGSRSASNM AI VDVKMVS GFIPLKPTVK MLERSNHVSR TEVSSNHVLI YLDKVSNQTL SLFFTVLQDV PVR DLKPAI VKVYDYYETD EFAIAEYNAP CSKDLGNA |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.1 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R2/2 / Material: COPPER/RHODIUM |
Vitrification | Cryogen name: ETHANE / Instrument: LEICA EM CPC |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number real images: 12143 / Average electron dose: 39.6 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.25 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 47775 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: OTHER |
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