2rjm: Difference between revisions

Revision as of 18:29, 6 February 2008

3Ig structure of titin domains I67-I69 E-to-A mutated variant

OverviewOverview

Myofibril elasticity, critical to muscle function, is dictated by the, intrasarcomeric filament titin, which acts as a molecular spring. To date, the molecular events underlying the mechanics of the folded titin chain, remain largely unknown. We have elucidated the crystal structure of the, 6-Ig fragment I65-I70 from the elastic I-band fraction of titin and, validated its conformation in solution using small angle x-ray scattering., The long-range properties of the chain have been visualized by electron, microscopy on a 19-Ig fragment and modeled for the full skeletal tandem., Results show that conserved Ig-Ig transition motifs generate high-order in, the structure of the filament, where conformationally stiff segments, interspersed with pliant hinges form a regular pattern of dynamic, super-motifs leading to segmental flexibility in the chain. Pliant hinges, support molecular shape rearrangements that dominate chain behavior at, moderate stretch, whereas stiffer segments predictably oppose high stretch, forces upon full chain extension. There, librational entropy can be, expected to act as an energy barrier to prevent Ig unfolding while, instead, triggering the unraveling of flanking springs formed by proline, glutamate, valine, and lysine (PEVK) sequences. We propose a mechanistic, model based on freely jointed rigid segments that rationalizes the, response to stretch of titin Ig-tandems according to molecular features.

About this StructureAbout this Structure

2RJM is a Protein complex structure of sequences from Oryctolagus cuniculus. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.

ReferenceReference

A regular pattern of Ig super-motifs defines segmental flexibility as the elastic mechanism of the titin chain., von Castelmur E, Marino M, Svergun DI, Kreplak L, Ucurum-Fotiadis Z, Konarev PV, Urzhumtsev A, Labeit D, Labeit S, Mayans O, Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1186-91. Epub 2008 Jan 22. PMID:18212128

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 ==Overview==
-The cellular function of the giant protein titin in striated muscle is a, major focus of scientific attention. Particularly, its role in passive, mechanics has been extensively investigated. In strong contrast, the, structural details of this filament are very poorly understood. To date, only a handful of atomic models from single domain components have become, available and data on poly-constructs are limited to scarce SAXS analyses., In this study, we examine the molecular parameters of poly-Ig tandems from, I-band titin relevant to muscle elasticity. We revisit conservation, patterns in domain and linker sequences of I-band modules and interpret, these in the light of available atomic structures of Ig domains from, muscle proteins. The emphasis is placed on features expected to affect, inter-domain arrangements. We examine the overall conformation of a 6Ig, fragment, I65-I70, from the skeletal I-band of soleus titin using SAXS and, electron microscopy approaches. The possible effect of highly conserved, glutamate groups at the linkers as well as the ionic strength of the, medium on the overall molecular parameters of this sample is investigated., Our findings indicate that poly-Ig tandems from I-band titin tend to adopt, extended arrangements with low or moderate intrinsic flexibility, independently of the specific features of linkers or component Ig domains, across constitutively- and differentially-expressed tandems. Linkers do, not appear to operate as free hinges so that lateral association of Ig, domains must occur infrequently in samples in solution, even that, inter-domain sequences of 4-5 residues length would well accommodate such, geometry. It can be expected that this principle is generally applicable, to all Ig-tandems from I-band titin.
+Myofibril elasticity, critical to muscle function, is dictated by the, intrasarcomeric filament titin, which acts as a molecular spring. To date, the molecular events underlying the mechanics of the folded titin chain, remain largely unknown. We have elucidated the crystal structure of the, 6-Ig fragment I65-I70 from the elastic I-band fraction of titin and, validated its conformation in solution using small angle x-ray scattering., The long-range properties of the chain have been visualized by electron, microscopy on a 19-Ig fragment and modeled for the full skeletal tandem., Results show that conserved Ig-Ig transition motifs generate high-order in, the structure of the filament, where conformationally stiff segments, interspersed with pliant hinges form a regular pattern of dynamic, super-motifs leading to segmental flexibility in the chain. Pliant hinges, support molecular shape rearrangements that dominate chain behavior at, moderate stretch, whereas stiffer segments predictably oppose high stretch, forces upon full chain extension. There, librational entropy can be, expected to act as an energy barrier to prevent Ig unfolding while, instead, triggering the unraveling of flanking springs formed by proline, glutamate, valine, and lysine (PEVK) sequences. We propose a mechanistic, model based on freely jointed rigid segments that rationalizes the, response to stretch of titin Ig-tandems according to molecular features.
 ==About this Structure==
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 ==Reference==
-Poly-Ig tandems from I-band titin share extended domain arrangements irrespective of the distinct features of their modular constituents., Marino M, Svergun DI, Kreplak L, Konarev PV, Maco B, Labeit D, Mayans O, J Muscle Res Cell Motil. 2005;26(6-8):355-65. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16341830 16341830]
+A regular pattern of Ig super-motifs defines segmental flexibility as the elastic mechanism of the titin chain., von Castelmur E, Marino M, Svergun DI, Kreplak L, Ucurum-Fotiadis Z, Konarev PV, Urzhumtsev A, Labeit D, Labeit S, Mayans O, Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1186-91. Epub 2008 Jan 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18212128 18212128]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Oryctolagus cuniculus]]
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 [[Category: titin]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb  6 15:31:56 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb  6 17:29:19 2008''