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|2klj, 10 NMR models ()|
|Gene:||CRYGD, CRYG4 (Homo sapiens)|
Solution Structure of gammaD-Crystallin with RDC and SAXS
Determining architectures of multicomponent proteins or protein complexes in solution is a challenging problem. Here we report a methodology that simultaneously uses residual dipolar couplings (RDC) and the small-angle X-ray scattering (SAXS) restraints to mutually orient subunits and define the global shape of multicomponent proteins and protein complexes. Our methodology is implemented in an efficient algorithm and demonstrated using five examples. First, we demonstrate the general approach with simulated data for the HIV-1 protease, a globular homodimeric protein. Second, we use experimental data to determine the structures of the two-domain proteins L11 and gammaD-Crystallin, in which the linkers between the domains are relatively rigid. Finally, complexes with K(d) values in the high micro- to millimolar range (weakly associating proteins), such as a homodimeric GB1 variant, and with K(d) values in the nanomolar range (tightly bound), such as the heterodimeric complex of the ILK ankyrin repeat domain (ARD) and PINCH LIM1 domain, respectively, are evaluated. Furthermore, the proteins or protein complexes that were determined using this method exhibit better solution structures than those obtained by either NMR or X-ray crystallography alone as judged based on the pair-distance distribution functions (PDDF) calculated from experimental SAXS data and back-calculated from the structures.
Determination of multicomponent protein structures in solution using global orientation and shape restraints., Wang J, Zuo X, Yu P, Byeon IJ, Jung J, Wang X, Dyba M, Seifert S, Schwieters CD, Qin J, Gronenborn AM, Wang YX, J Am Chem Soc. 2009 Aug 5;131(30):10507-15. PMID:19722627
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[CRGD_HUMAN] Defects in CRYGD are a cause of cataract autosomal dominant (ADC) [MIM:604219]. Cataract is an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. Cataract is the most common treatable cause of visual disability in childhood. Defects in CRYGD are the cause of cataract congenital non-nuclear polymorphic autosomal dominant (CCP) [MIM:601286]; also known as polymorphic congenital cataract. A congenital cataract characterized by a non-progressive phenotype and partial opacity that has a variable location between the fetal nucleus of the lens and the equator. The fetal nucleus is normal. The opacities are irregular and look similar to a bunch of grapes and may be present simultaneously in different lens layers. Defects in CRYGD are the cause of cataract congenital cerulean type 3 (CCA3) [MIM:608983]; also known as congenital cataract blue dot type 3. A cerulean form of autosomal dominant congenital cataract. Cerulean cataract is characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. Defects in CRYGD are the cause of cataract crystalline aculeiform (CACA) [MIM:115700]. A congenital crystalline cataract characterized by fiberglass-like or needle-like crystals projecting in different directions, through or close to the axial region of the lens. The opacity causes a variable degree of vision loss.
[CRGD_HUMAN] Crystallins are the dominant structural components of the vertebrate eye lens.
About this Structure
- Wang J, Zuo X, Yu P, Byeon IJ, Jung J, Wang X, Dyba M, Seifert S, Schwieters CD, Qin J, Gronenborn AM, Wang YX. Determination of multicomponent protein structures in solution using global orientation and shape restraints. J Am Chem Soc. 2009 Aug 5;131(30):10507-15. PMID:19722627 doi:10.1021/ja902528f
- Jung J, Byeon IJ, Wang Y, King J, Gronenborn A. The structure of the cataract causing P23T mutant of HgD crystallin exhibits local distinctive conformational and dynamic changes. Biochemistry. 2009 Feb 13. PMID:19216553 doi:10.1021/bi802292q
- ↑ Stephan DA, Gillanders E, Vanderveen D, Freas-Lutz D, Wistow G, Baxevanis AD, Robbins CM, VanAuken A, Quesenberry MI, Bailey-Wilson J, Juo SH, Trent JM, Smith L, Brownstein MJ. Progressive juvenile-onset punctate cataracts caused by mutation of the gammaD-crystallin gene. Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1008-12. PMID:9927684
- ↑ Pande A, Pande J, Asherie N, Lomakin A, Ogun O, King JA, Lubsen NH, Walton D, Benedek GB. Molecular basis of a progressive juvenile-onset hereditary cataract. Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):1993-8. PMID:10688888 doi:10.1073/pnas.040554397
- ↑ Wang B, Yu C, Xi YB, Cai HC, Wang J, Zhou S, Zhou S, Wu Y, Yan YB, Ma X, Xie L. A novel CRYGD mutation (p.Trp43Arg) causing autosomal dominant congenital cataract in a Chinese family. Hum Mutat. 2011 Jan;32(1):E1939-47. doi: 10.1002/humu.21386. PMID:21031598 doi:10.1002/humu.21386
- ↑ Messina-Baas OM, Gonzalez-Huerta LM, Cuevas-Covarrubias SA. Two affected siblings with nuclear cataract associated with a novel missense mutation in the CRYGD gene. Mol Vis. 2006 Aug 24;12:995-1000. PMID:16943771
- ↑ Plotnikova OV, Kondrashov FA, Vlasov PK, Grigorenko AP, Ginter EK, Rogaev EI. Conversion and compensatory evolution of the gamma-crystallin genes and identification of a cataractogenic mutation that reverses the sequence of the human CRYGD gene to an ancestral state. Am J Hum Genet. 2007 Jul;81(1):32-43. Epub 2007 May 16. PMID:17564961 doi:S0002-9297(07)62814-6
- ↑ Heon E, Priston M, Schorderet DF, Billingsley GD, Girard PO, Lubsen N, Munier FL. The gamma-crystallins and human cataracts: a puzzle made clearer. Am J Hum Genet. 1999 Nov;65(5):1261-7. PMID:10521291 doi:10.1086/302619