The worldwide Protein Data Bank (wwPDB): ensuring a single, uniform archive of PDB data

Berman, Helen M.; Henrick, Kim; Nakamura, Haruki; Markley, John L.

doi:10.1093/nar/gkl971

Cited by 1,033 publications

(891 citation statements)

References 18 publications

(12 reference statements)

Supporting

Mentioning

884

Contrasting

Unclassified

Order By: Relevance

“…To do this, we manually aligned the Reelin sequence (UniProt: P78509) according to its component repeats by using Jalview. 23 Two crystal structures (PDB: 2DDU, 2E26) 24 were used as starting points for modeling with the HOMER server. The models were analyzed with the ConSurf 25 server, and figures were drawn with ESPript 26 for sequence alignments and with PyMol (DeLano Scientific) for structures.…”

mentioning

confidence: 99%

Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

Dazzo

Fanciulli²,

Serioli

et al. 2015

The American Journal of Human Genetics

View full text Add to dashboard Cite

Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic epilepsy syndrome clinically characterized by focal seizures with prominent auditory symptoms. ADLTE is genetically heterogeneous, and mutations in LGI1 account for fewer than 50% of affected families. Here, we report the identification of causal mutations in reelin (RELN) in seven ADLTE-affected families without LGI1 mutations. We initially investigated 13 ADLTE-affected families by performing SNP-array linkage analysis and whole-exome sequencing and identified three heterozygous missense mutations co-segregating with the syndrome. Subsequent analysis of 15 small ADLTE-affected families revealed four additional missense mutations. 3D modeling predicted that all mutations have structural effects on protein-domain folding. Overall, RELN mutations occurred in 7/40 (17.5%) ADLTE-affected families. RELN encodes a secreted protein, Reelin, which has important functions in both the developing and adult brain and is also found in the blood serum. We show that ADLTE-related mutations significantly decrease serum levels of Reelin, suggesting an inhibitory effect of mutations on protein secretion. We also show that Reelin and LGI1 co-localize in a subset of rat brain neurons, supporting an involvement of both proteins in a common molecular pathway underlying ADLTE. Homozygous RELN mutations are known to cause lissencephaly with cerebellar hypoplasia. Our findings extend the spectrum of neurological disorders associated with RELN mutations and establish a link between RELN and LGI1, which play key regulatory roles in both the developing and adult brain.Temporal-lobe epilepsy is the most common type of focal epilepsy. It is sometimes associated with structural brain lesions, but genetic forms have also been described. Familial temporal-lobe epilepsy comprises two genetically distinct syndromes: familial mesial temporal-lobe epilepsy (FMTLE [MIM: 611630]) 1 and autosomal-dominant lateral temporal epilepsy (ADLTE [MIM: 600512]), also named autosomal-dominant partial epilepsy with auditory features (ADPEAF). 2 ADLTE is a well-defined epileptic syndrome clinically characterized by focal seizures with prominent auditory and/or aphasic symptoms, normal brain MRI, and relatively benign evolution. 2,3 Its inheritance pattern is autosomal dominant with reduced penetrance (around 70%). Mutations associated with ADLTE are found in leucine-rich, glioma inactivated 1 (LGI1 [MIM: 604619]) 4-6 in 30%-50% of ADLTE-affected families. 3,7,8 Other genes harboring ADLTE-causing mutations are unknown.LGI1 is expressed mainly in neurons, particularly in the neocortex and limbic regions, 4,9 and its protein product, LGI1, is secreted. 9 LGI1 has been implicated in the transmission of K þ and AMPA synaptic currents 10,11 and in the regulation of post-natal maturation of cortical excitatory synapses and dendrite pruning. 12 However, it is not known which of these functions underlies ADLTE. Identification of additional genes whose mutations cause ADLTE will help to clarify the pathoge...

show abstract

mentioning

confidence: 99%

Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

Dazzo

Fanciulli²,

Serioli

et al. 2015

The American Journal of Human Genetics

View full text Add to dashboard Cite

show abstract

“…It is the azimuthal angle between n i and the projection of u i on the normal plane spanned by (n i , b i ). Under the frame rotation (8) we have…”

Section: Ii: Methodsmentioning

confidence: 99%

“…Full crystallographic information of the experimental λ-repressor structure that we use in our investigation is available in Protein Data Bank (PDB) [8] under the code 1LMB. This structure is a homo-dimer with 92 residues in each of the two monomers.…”

Section: I: Introductionmentioning

confidence: 99%

“…In particular, the temporal ordering of loop formation appears to be the decisive factor for the protein's ability to reach its native fold. If solitons form in a wrong order the protein may misfold.Full crystallographic information of the experimental λ-repressor structure that we use in our investigation is available in Protein Data Bank (PDB) [8] under the code 1LMB. This structure is a homo-dimer with 92 residues in each of the two monomers.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Solitons and collapse in theλ−repressor protein

2012

View full text Add to dashboard Cite

The enterobacteria lambda phage is a paradigm temperate bacteriophage. Its lysogenic and lytic life cycles echo competition between the DNA binding λ-repressor (CI) and CRO proteins. Here we scrutinize the structure, stability and folding pathways of the λ-repressor protein, that controls the transition from the lysogenic to the lytic state. We first investigate the super-secondary helix-loophelix composition of its backbone. We use a discrete Frenet framing to resolve the backbone spectrum in terms of bond and torsion angles. Instead of four, there appears to be seven individual loops. We model the putative loops using an explicit soliton Ansatz. It is based on the standard soliton profile of the continuum nonlinear Schrödinger equation. The accuracy of the Ansatz far exceeds the B-factor fluctuation distance accuracy of the experimentally determined protein configuration. We then investigate the folding pathways and dynamics of the λ-repressor protein. We introduce a coarse-grained energy function to model the backbone in terms of the Cα atoms and the side-chains in terms of the relative orientation of the C β atoms. We describe the folding dynamics in terms of relaxation dynamics, and find that the folded configuration can be reached from a very generic initial configuration. We conclude that folding is dominated by the temporal ordering of soliton formation. In particular, the third soliton should appear before the first and second. Otherwise, the DNA binding turn does not acquire its correct structure. We confirm the stability of the folded configuration by repeated heating and cooling simulations. I: INTRODUCTIONThe transition between the lysogenic and the lytic state in bacteriophage λ infected E. coli cell is the paradigm genetic switch mechanism. It is described in numerous molecular biology textbooks and review articles [1]- [7]. The interplay between the lysogeny maintaining λ-repressor (CI) protein and the CRO regulator protein that controls the transition to the lytic state is a simple model for more complex regulatory networks, including those that can lead to cancer in humans.In the present article we describe the physical properties of the λ-repressor protein, that controls the lysogenic-to-lytic transition. We investigate in detail the stability of its native conformation, the dynamics of the folding process, and the landscape of folding pathways. We find that the folded configuration displays a structure which is unique among all known protein structures. We also conclude that the folding pathways are entirely dominated by the loop regions. In particular, the temporal ordering of loop formation appears to be the decisive factor for the protein's ability to reach its native fold. If solitons form in a wrong order the protein may misfold.Full crystallographic information of the experimental λ-repressor structure that we use in our investigation is available in Protein Data Bank (PDB) [8] under the code 1LMB. This structure is a homo-dimer with 92 residues in each of the two monomers. It maintain...

show abstract

“…Because crystals of macromolecules typically diffract only to modest resolution, the use of B iso has been particularly common in structural models for macromolecules. Indeed, the standard ATOM record for structures archived in the Protein Data Bank (PDB) contains a field for a single 'Temperature factor' (Berman et al, 2007), and many software tools that manipulate PDB files expect an isotropic ADP to be provided here.…”

Section: The Origin Of B Eqmentioning

confidence: 99%

SomeB_eqare more equivalent than others

Merritt

2011

Acta Cryst Sect A

View full text Add to dashboard Cite

Crystallographic structural models for macromolecules have typically included an isotropic displacement parameter B iso for each atom. In cases where the structural model instead includes anisotropic displacement parameters U ij , the derived quantity B eq can be substituted for B iso for many purposes. B eq is not, however, the best predictor of the value B iso that would hypothetically have been obtained by direct refinement of an isotropic model. A new entity B est is proposed that represents an estimate for B iso that minimizes the KullbackLeibler divergence from a paired anisotropic model. In general B est =B eq < 1, with the difference between the two values becoming larger for atoms that are more anisotropic. Although this difference does not affect direct refinement of either isotropic or anisotropic models, it is relevant to any analysis that compares isotropic and anisotropic models of the same underlying structure. In particular, it may lead to improved selection of multi-group TLS models based on analysis of an initial isotropic refinement.

show abstract

The worldwide Protein Data Bank (wwPDB): ensuring a single, uniform archive of PDB data

Cited by 1,033 publications

References 18 publications

Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

Solitons and collapse in theλ−repressor protein

SomeB_eqare more equivalent than others

Contact Info

Product

Resources

About

The worldwide Protein Data Bank (wwPDB): ensuring a single, uniform archive of PDB data

Cited by 1,033 publications

References 18 publications

Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

Solitons and collapse in theλ−repressor protein

SomeBeqare more equivalent than others

Contact Info

Product

Resources

About

SomeB_eqare more equivalent than others