Wikipedia

Ankyrin

Ankyrinsare a family of proteins that mediate the attachment ofintegral membrane proteinsto thespectrin-actinbased membrane cytoskeleton.[2]Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins. This linkage is required to maintain the integrity of theplasma membranesand to anchor specificion channels,ion exchangersandion transportersin the plasma membrane. The name is derived from theGreekwordἄγκυρα(ankyra) for "anchor".

ANK1, erythrocytic
Ribbon diagramof a fragment of the membrane-binding domain of ankyrin R.[1]
Identifiers
SymbolANK1
Alt. symbolsAnkyrinR, Band2.1
NCBI gene286
HGNC492
OMIM182900
PDB1N11
RefSeqNM_000037
UniProtP16157
Other data
LocusChr. 8p21.1-11.2
Search for
StructuresSwiss-model
DomainsInterPro
Ankyrin repeat
Identifiers
SymbolAnk
PfamPF00023
InterProIPR002110
SMARTSM00248
PROSITEPDOC50088
SCOP21awc/SCOPe/SUPFAM
Available protein structures:
Pfam structures/ECOD
PDBRCSB PDB;PDBe;PDBj
PDBsumstructure summary
ANK2, neuronal
Identifiers
SymbolANK2
Alt. symbolsAnkyrinB
NCBI gene287
HGNC493
OMIM106410
RefSeqNM_001148
UniProtQ01484
Other data
LocusChr. 4q25-q27
Search for
StructuresSwiss-model
DomainsInterPro
ANK3, node of Ranvier
Identifiers
SymbolANK3
Alt. symbolsAnkyrinG
NCBI gene288
HGNC494
OMIM600465
RefSeqNM_020987
UniProtQ12955
Other data
LocusChr. 10q21
Search for
StructuresSwiss-model
DomainsInterPro

Structure

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Ankyrins contain four functionaldomains:anN-terminaldomain that contains 24 tandemankyrin repeats,a central domain that binds tospectrin,a death domain that binds to proteins involved inapoptosis,and aC-terminalregulatory domain that is highly variable between different ankyrin proteins.[2]

Membrane protein recognition

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The 24 tandem ankyrin repeats are responsible for the recognition of a wide range of membrane proteins. These 24 repeats contain 3 structurally distinct binding sites ranging from repeat 1-14. These binding sites are quasi-independent of each other and can be used in combination. The interactions the sites use to bind to membrane proteins are non-specific and consist of: hydrogen bonding, hydrophobic interactions and electrostatic interactions. These non-specific interactions give ankyrin the property to recognise a large range of proteins as the sequence doesn't have to be conserved, just the properties of theamino acids.The quasi-independence means that if a binding site is not used, it won't have a large effect on the overall binding. These two properties in combination give rise to large repertoire of proteins ankyrin can recognise.

Subtypes

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Ankyrins are encoded by three genes (ANK1,ANK2andANK3) in mammals. Each gene in turn produces multiple proteins throughalternative splicing.

ANK1

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TheANK1gene encodes the AnkyrinR proteins. AnkyrinR was first characterized in human erythrocytes, where this ankyrin was referred to as erythrocyte ankyrin or band2.1.[3]AnkyrinR enables erythrocytes to resist shear forces experienced in the circulation. Individuals with reduced or defective ankyrinR have a form ofhemolytic anemiatermedhereditary spherocytosis.[4]In erythrocytes, AnkyrinR links the membrane skeleton to theCl−/HCO3−anion exchanger.[5]

Ankyrin 1 links membrane receptorCD44to theinositol triphosphate receptorand thecytoskeleton.[6]

It has been suggested that Ankyrin 1 interacts withKAHRP(shown via selective pull-downs,SPRandELISA).[7]

ANK2

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LeftPalmitoylation(red) anchors Ankyrin G to the plasma membrane.RightClose up. Palmitoyl residue in yellow.

Subsequently, ankyrinB proteins (products of theANK2gene[8]) were identified in brain and muscle. AnkyrinB and AnkyrinG proteins are required for the polarized distribution of many membrane proteins including the Na+/K+ATPase, the voltage gated Na+channel and the Na+/Ca2+exchanger.

ANK3

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AnkyrinG proteins (products of theANK3gene[9]) were identified in epithelial cells and neurons. A large-scale genetic analysis conducted in 2008 shows the possibility thatANK3is involved inbipolar disorder.[10][11]

See also

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  • DARPin(designed ankyrin repeat protein), an engineered antibody mimetic based on the structure of ankyrin repeats

References

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  1. ^PDB:1N11​;Michaely P, Tomchick DR, Machius M, Anderson RG (December 2002)."Crystal structure of a 12 ANK repeat stack from human ankyrinR".The EMBO Journal.21(23): 6387–96.doi:10.1093/emboj/cdf651.PMC136955.PMID12456646.
  2. ^abBennett V, Baines AJ (July 2001)."Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues".Physiological Reviews.81(3): 1353–92.doi:10.1152/physrev.2001.81.3.1353.PMID11427698.S2CID15307181.
  3. ^Bennett V, Stenbuck PJ (April 1979)."Identification and partial purification of ankyrin, the high affinity membrane attachment site for human erythrocyte spectrin".The Journal of Biological Chemistry.254(7): 2533–41.doi:10.1016/S0021-9258(17)30254-5.PMID372182.
  4. ^Lux SE, Tse WT, Menninger JC, John KM, Harris P, Shalev O, Chilcote RR, Marchesi SL, Watkins PC, Bennett V (June 1990). "Hereditary spherocytosis associated with deletion of human erythrocyte ankyrin gene on chromosome 8".Nature.345(6277): 736–9.Bibcode:1990Natur.345..736L.doi:10.1038/345736a0.PMID2141669.S2CID4334791.
  5. ^Bennett V, Stenbuck PJ (August 1979). "The membrane attachment protein for spectrin is associated with band 3 in human erythrocyte membranes".Nature.280(5722): 468–73.Bibcode:1979Natur.280..468B.doi:10.1038/280468a0.PMID379653.S2CID4268702.
  6. ^Singleton PA, Bourguignon LY (April 2004). "CD44 interaction with ankyrin and IP3 receptor in lipid rafts promotes hyaluronan-mediated Ca2+ signaling leading to nitric oxide production and endothelial cell adhesion and proliferation".Experimental Cell Research.295(1): 102–18.doi:10.1016/j.yexcr.2003.12.025.PMID15051494.
  7. ^Weng H, Guo X, Papoin J, Wang J, Coppel R, Mohandas N, An X (January 2014)."Interaction of Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) with erythrocyte ankyrin R is required for its attachment to the erythrocyte membrane".Biochimica et Biophysica Acta (BBA) - Biomembranes.1838(1 Pt B): 185–92.doi:10.1016/j.bbamem.2013.09.014.PMC4403245.PMID24090929.
  8. ^Schott JJ, Charpentier F, Peltier S, Foley P, Drouin E, Bouhour JB, Donnelly P, Vergnaud G, Bachner L, Moisan JP (November 1995)."Mapping of a gene for long QT syndrome to chromosome 4q25-27".American Journal of Human Genetics.57(5): 1114–22.PMC1801360.PMID7485162.
  9. ^Kapfhamer D, Miller DE, Lambert S, Bennett V, Glover TW, Burmeister M (May 1995). "Chromosomal localization of the ankyrinG gene (ANK3/Ank3) to human 10q21 and mouse 10".Genomics.27(1): 189–91.doi:10.1006/geno.1995.1023.PMID7665168.
  10. ^Ferreira MA, O'Donovan MC, Meng YA, Jones IR, Ruderfer DM, Jones L, et al. (September 2008)."Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder".Nature Genetics.40(9): 1056–8.doi:10.1038/ng.209.PMC2703780.PMID18711365.
  11. ^"Channeling Mental Illness: GWAS Links Ion Channels, Bipolar Disorder".Schizophrenia Research Forum: News.schizophreniaforum.org. 2008-08-19. Archived fromthe originalon 2010-12-18.Retrieved2008-08-21.
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