Crystal Structure of Truncated Human BetaB1-crystallin

Overview

Journal Protein Sci

Specialty Biochemistry

Date 2003 Oct 24

PMID 14573871

Citations 45

Authors

Rob L M van Montfort

Orval A Bateman

Nicolette H Lubsen

Christine Slingsby

Affiliations

Soon will be listed here.

Abstract

Crystallins are long-lived proteins packed inside eye lens fiber cells that are essential in maintaining the transparency and refractive power of the eye lens. Members of the two-domain betagamma-crystallin family assemble into an array of oligomer sizes, forming intricate higher-order networks in the lens cell. Here we describe the 1.4 angstroms resolution crystal structure of a truncated version of human betaB1 that resembles an in vivo age-related truncation. The structure shows that unlike its close homolog, betaB2-crystallin, the homodimer is not domain swapped, but its domains are paired intramolecularly, as in more distantly related monomeric gamma-crystallins. However, the four-domain dimer resembles one half of the crystallographic bovine betaB2 tetramer and is similar to the engineered circular permuted rat betaB2. The crystal structure shows that the truncated betaB1 dimer is extremely well suited to form higher-order lattice interactions using its hydrophobic surface patches, linker regions, and sequence extensions.

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References

David L, Lampi K, Lund A, Smith J . The sequence of human betaB1-crystallin cDNA allows mass spectrometric detection of betaB1 protein missing portions of its N-terminal extension. J Biol Chem. 1996; 271(8):4273-9. DOI: 10.1074/jbc.271.8.4273. View

Bax B, Lapatto R, Nalini V, Driessen H, Lindley P, Mahadevan D . X-ray analysis of beta B2-crystallin and evolution of oligomeric lens proteins. Nature. 1990; 347(6295):776-80. DOI: 10.1038/347776a0. View

Wistow G, Piatigorsky J . Lens crystallins: the evolution and expression of proteins for a highly specialized tissue. Annu Rev Biochem. 1988; 57:479-504. DOI: 10.1146/annurev.bi.57.070188.002403. View

Bateman O, Sarra R, van Genesen S, KAPPE G, Lubsen N, Slingsby C . The stability of human acidic beta-crystallin oligomers and hetero-oligomers. Exp Eye Res. 2003; 77(4):409-22. DOI: 10.1016/s0014-4835(03)00173-8. View

Lampi K, Kim Y, Bachinger H, Boswell B, Lindner R, Carver J . Decreased heat stability and increased chaperone requirement of modified human betaB1-crystallins. Mol Vis. 2002; 8:359-66. View

Ma Z, Hanson S, Lampi K, David L, Smith D, Smith J . Age-related changes in human lens crystallins identified by HPLC and mass spectrometry. Exp Eye Res. 1998; 67(1):21-30. DOI: 10.1006/exer.1998.0482. View

Berbers G, Boerman O, Bloemendal H, de Jong W . Primary gene products of bovine beta-crystallin and reassociation behavior of its aggregates. Eur J Biochem. 1982; 128(2-3):495-502. DOI: 10.1111/j.1432-1033.1982.tb06992.x. View

Horwitz J . The function of alpha-crystallin in vision. Semin Cell Dev Biol. 2000; 11(1):53-60. DOI: 10.1006/scdb.1999.0351. View

Lapatto R, Nalini V, Bax B, Driessen H, Lindley P, Blundell T . High resolution structure of an oligomeric eye lens beta-crystallin. Loops, arches, linkers and interfaces in beta B2 dimer compared to a monomeric gamma-crystallin. J Mol Biol. 1991; 222(4):1067-83. DOI: 10.1016/0022-2836(91)90594-v. View

10.

Jones T, Zou J, Cowan S, Kjeldgaard M . Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991; 47 ( Pt 2):110-9. DOI: 10.1107/s0108767390010224. View

11.

Jaenicke R, Slingsby C . Lens crystallins and their microbial homologs: structure, stability, and function. Crit Rev Biochem Mol Biol. 2001; 36(5):435-99. DOI: 10.1080/20014091074237. View

12.

van Montfort R, Basha E, Friedrich K, Slingsby C, Vierling E . Crystal structure and assembly of a eukaryotic small heat shock protein. Nat Struct Biol. 2001; 8(12):1025-30. DOI: 10.1038/nsb722. View

13.

Bindels J, Koppers A, Hoenders H . Structural aspects of bovine beta-crystallins: physical characterization including dissociation-association behavior. Exp Eye Res. 1981; 33(3):333-43. DOI: 10.1016/s0014-4835(81)80056-5. View

14.

Wright G, Basak A, Wieligmann K, Mayr E, Slingsby C . Circular permutation of betaB2-crystallin changes the hierarchy of domain assembly. Protein Sci. 1998; 7(6):1280-5. PMC: 2144035. DOI: 10.1002/pro.5560070602. View

15.

Werten P, Lindner R, Carver J, de Jong W . Formation of betaA3/betaB2-crystallin mixed complexes: involvement of N- and C-terminal extensions. Biochim Biophys Acta. 1999; 1432(2):286-92. DOI: 10.1016/s0167-4838(99)00123-5. View

16.

Perrakis A, Morris R, Lamzin V . Automated protein model building combined with iterative structure refinement. Nat Struct Biol. 1999; 6(5):458-63. DOI: 10.1038/8263. View

17.

Lubsen N, Aarts H, Schoenmakers J . The evolution of lenticular proteins: the beta- and gamma-crystallin super gene family. Prog Biophys Mol Biol. 1988; 51(1):47-76. DOI: 10.1016/0079-6107(88)90010-7. View

18.

Lampi K, Ma Z, Hanson S, Azuma M, Shih M, Shearer T . Age-related changes in human lens crystallins identified by two-dimensional electrophoresis and mass spectrometry. Exp Eye Res. 1998; 67(1):31-43. DOI: 10.1006/exer.1998.0481. View

19.

Ajaz M, Ma Z, Smith D, Smith J . Size of human lens beta-crystallin aggregates are distinguished by N-terminal truncation of betaB1. J Biol Chem. 1997; 272(17):11250-5. DOI: 10.1074/jbc.272.17.11250. View

20.

Slingsby C, Bateman O . Quaternary interactions in eye lens beta-crystallins: basic and acidic subunits of beta-crystallins favor heterologous association. Biochemistry. 1990; 29(28):6592-9. DOI: 10.1021/bi00480a007. View