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Structure paper

TitleStructure, dynamics and assembly of the ankyrin complex on human red blood cell membrane.
Journal, issue, pagesNat Struct Mol Biol, Vol. 29, Issue 7, Page 698-705, Year 2022
Publish dateJun 2, 2022
AuthorsXian Xia / Shiheng Liu / Z Hong Zhou /
PubMed AbstractThe cytoskeleton of a red blood cell (RBC) is anchored to the cell membrane by the ankyrin complex. This complex is assembled during RBC genesis and comprises primarily band 3, protein 4.2 and ...The cytoskeleton of a red blood cell (RBC) is anchored to the cell membrane by the ankyrin complex. This complex is assembled during RBC genesis and comprises primarily band 3, protein 4.2 and ankyrin, whose mutations contribute to numerous human inherited diseases. High-resolution structures of the ankyrin complex have been long sought-after to understand its assembly and disease-causing mutations. Here, we analyzed native complexes on the human RBC membrane by stepwise fractionation. Cryo-electron microscopy structures of nine band-3-associated complexes reveal that protein 4.2 stabilizes the cytoplasmic domain of band 3 dimer. In turn, the superhelix-shaped ankyrin binds to this protein 4.2 via ankyrin repeats (ARs) 6-13 and to another band 3 dimer via ARs 17-20, bridging two band 3 dimers in the ankyrin complex. Integration of these structures with both prior data and our biochemical data supports a model of ankyrin complex assembly during erythropoiesis and identifies interactions essential for the mechanical stability of RBC.
External linksNat Struct Mol Biol / PubMed:35655099 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 8.5 Å
Structure data

EMDB-26142, PDB-7tvz:
Cryo-EM structure of human band 3-protein 4.2 complex in diagonal conformation
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-26143: Membrane domain of band3-protein 4.2 complex in diagonal conformation
Method: EM (single particle) / Resolution: 3.26 Å

EMDB-26144: Cytoplasmic domain of band 3-protein 4.2 complex in diagonal conformation
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-26145: Cryo-EM structure of human band 3-protein 4.2 complex in a loosely-bound conformation
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-26146, PDB-7tw0:
Cryo-EM structure of human band 3-protein 4.2 complex in vertical conformation
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-26147, PDB-7tw1:
Cryo-EM structure of human band 3-protein 4.2 complex (B2P2vertical)
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-26148, PDB-7tw2:
Cryo-EM structure of human band 3 dimer from red blood cell
Method: EM (single particle) / Resolution: 4.8 Å

EMDB-26149, PDB-7tw3:
Cryo-EM structure of human ankyrin complex (B2P1A1) from red blood cell
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-26150: Cytoplasmic domain of ankyrin complex (B2P1A1)
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-26151, PDB-7tw5:
Cryo-EM structure of human ankyrin complex (B2P1A2) from red blood cell
Method: EM (single particle) / Resolution: 5.7 Å

EMDB-26152: Cytoplasmic domain of ankyrin complex (B2P1A2)
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-26153, PDB-7tw6:
Cryo-EM structure of human ankyrin complex (B4P1A1) from red blood cell
Method: EM (single particle) / Resolution: 5.6 Å

EMDB-26154: Cryo-EM structure of human ankyrin complex (B2P1A1)2
Method: EM (single particle) / Resolution: 8.5 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-LMT:
DODECYL-BETA-D-MALTOSIDE / detergent*YM

ChemComp-CLR:
CHOLESTEROL

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • human (human)
KeywordsMEMBRANE PROTEIN / Red blood cell / Ankyrin complex / band 3 / protein 4.2

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