Papers by Manuel M Sánchez del Pino
Biochemistry Usa, 1997
... Manuel M. Sánchez del Pino and Alan R. Fersht*. MRC Unit for Protein Function and Design ... ... more ... Manuel M. Sánchez del Pino and Alan R. Fersht*. MRC Unit for Protein Function and Design ... Although TIM barrel proteins appear to have a single domain, folding studies revealed that they behave as if there are two folding domains (Eder & Kirschner, 1992; Miles et al., 1982). ...
Nature structural biology, 1999
We have analyzed the folding pathway of the tetramerization domain of the tumor suppressor protei... more We have analyzed the folding pathway of the tetramerization domain of the tumor suppressor protein p53. Structures of transition states were determined from phi-values for 25 mutations, including leucine to norvaline, and the analysis encompassed nearly every residue in the domain. Denatured monomers fold and dimerize, through a transition state with little native structure, to form a transient, highly structured dimeric intermediate. The intermediate dimerizes, through a native-like transition state with the primary dimers fully folded but with interdimer interactions only partially formed, to form the native tetramer as a 'dimer of dimers'.
PLoS ONE, 2012
The lipase produced by Burkholderia glumae folds spontaneously into an inactive near-native state... more The lipase produced by Burkholderia glumae folds spontaneously into an inactive near-native state and requires a periplasmic chaperone to reach its final active and secretion-competent fold. The B. glumae lipase-specific foldase (Lif) is classified as a member of the steric-chaperone family of which the propeptides of a-lytic protease and subtilisin are the best known representatives. Steric chaperones play a key role in conferring kinetic stability to proteins. However, until present there was no solid experimental evidence that Lif-dependent lipases are kinetically trapped enzymes. By combining thermal denaturation studies with proteolytic resistance experiments and the description of distinct folding intermediates, we demonstrate that the native lipase has a kinetically stable conformation. We show that a newly discovered molten globulelike conformation has distinct properties that clearly differ from those of the near-native intermediate state. The folding fingerprint of Lif-dependent lipases is put in the context of the protease-prodomain system and the comparison reveals clear differences that render the lipase-Lif systems unique. Limited proteolysis unveils structural differences between the near-native intermediate and the native conformation and sets the stage to shed light onto the nature of the kinetic barrier. Citation: Pauwels K, Sanchez del Pino MM, Feller G, Van Gelder P (2012) Decoding the Folding of Burkholderia glumae Lipase: Folding Intermediates En Route to Kinetic Stability. PLoS ONE 7(5): e36999.
Stem Cell Reviews and Reports, 2012
PLoS ONE, 2011
Background: Although the AIB1 oncogene has an important role during the early phase of the cell c... more Background: Although the AIB1 oncogene has an important role during the early phase of the cell cycle as a coactivator of E2F1, little is known about its function during mitosis.
Journal of Biological Chemistry, 1995
American Journal of …, 2003
Cardiotrophin-1 (CT-1) is a cytokine of the interleukin-6 family, essentially of cardiac origin, ... more Cardiotrophin-1 (CT-1) is a cytokine of the interleukin-6 family, essentially of cardiac origin, that can be detected in plasma. It is produced in conditions of myocardial biomechanical stress and acts as a cardiomyocyte survival factor. Provided that, in the ...
Biochemistry, 1997
The folding of the enzyme indole-3-glycerol-phosphate synthase (IGPS), a member of the (alpha/bet... more The folding of the enzyme indole-3-glycerol-phosphate synthase (IGPS), a member of the (alpha/beta)8 fold family, has been studied. At least two folding intermediates have been detected using spectroscopic and activity measurements in combination with gel filtration chromatography. These two intermediates are produced by parallel pathways of a nonsequential unfolding mechanism rather than being consecutive steps in a sequential process. One intermediate can be detected in unfolding experiments because it is kinetically trapped in that conformation, but it is not observed in refolding experiments. It has spectroscopic and hydrodynamic properties very similar to those of the native protein, but it is inactive. The other intermediate could not be characterized because it either aggregates or unfolds under our experimental conditions and could not be isolated chromatographically.
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. AD brains are chara... more Alzheimer's disease (AD) is the most common cause of dementia in the elderly. AD brains are characterized by the presence of neurofibrillary tangles (NFTs) and neuritic plaques. NFTs are constituted of paired helical filaments, which are structurally composed by assembled hyperphosphorylated and truncated tau polypeptides. To date, the integral constituents of NFTs remain unknown mainly due to the high insolubility of NFTs. The aim of this study was to identify by tandem mass spectrometry, the polypeptides contained in both isolated NFTs by laser capture microdissection and total homogenates, using tissue sections from paraformaldehyde-fixed AD brains. In the first case, we isolated 2,000 NFTs from tissue samples of hippocampus from each of the three Mexican AD brains used in our study. These were previously stained with anti-hyperphosphorylated tau AT-100 antibodies. After the removal of paraformaldehyde and delipidation with organic solvents, we tested three solubilization methods. We identified 102 polypeptides from total homogenates and 41 from isolated NFTs. We selected UCH-L1, transferrin, and GAPDH polypeptides to be studied by immunofluorescence and confocal microscopy. Only UCH-L1 and GAPDH colocalized with hyperphosphorylated tau in NFTs.
Journal of Proteome Research, 2014
The Spanish team of the Human Proteome Project (SpHPP) marked the annotation of Chr16 and data an... more The Spanish team of the Human Proteome Project (SpHPP) marked the annotation of Chr16 and data analysis as one of its priorities. Precise annotation of Chromosome 16 proteins according to C-HPP criteria is presented. Moreover, Human Body Map 2.0 RNA-Seq and Encyclopedia of DNA Elements (ENCODE) data sets were used to obtain further information relative to cell/tissue specific chromosome 16 coding gene expression patterns and to infer the presence of missing proteins. Twenty-four shotgun 2D-LC−MS/MS and gel/LC−MS/MS MIAPE compliant experiments, representing 41% coverage of chromosome 16 proteins, were performed. Furthermore, mapping of large-scale multicenter mass spectrometry data sets from CCD18, MCF7, Jurkat, and Ramos cell lines into RNA-Seq data allowed further insights relative to correlation of chromosome 16 transcripts and proteins. Detection and quantification of chromosome 16 proteins in biological matrices by SRM procedures are also primary goals of the SpHPP. Two strategies were undertaken: one focused on known proteins, taking advantage of MS data already available, and the second, aimed at the detection of the missing proteins, is based on the expression of recombinant proteins to gather MS information and optimize SRM methods that will be used in real biological samples. SRM methods for 49 known proteins and for recombinant forms of 24 missing proteins are reported in this study.
not my papers by Manuel M Sánchez del Pino
Journal of Differential Equations, 2007
We study the existence of radial ground state solutions for the problem −div ∇u
Journal of Differential Equations, 2002
This paper deals with the slightly super-critical elliptic problem
Journal of Differential Equations, 2006
We consider the problem of Ambrosetti-Prodi type
Journal of Differential Equations, 2003
In this paper, we consider the Brezis-Nirenberg problem in dimension N ≥ 4, in the supercritical ... more In this paper, we consider the Brezis-Nirenberg problem in dimension N ≥ 4, in the supercritical case. We prove that if the exponent gets close to N +2 N −2 and if, simultaneously, the bifurcation parameter tends to zero at the appropriate rate, then there are radial solutions which behave like a superposition of bubbles, namely solutions of the form
Journal of Differential Equations, 2013
We consider the semilinear equation
Journal de Mathématiques Pures et Appliquées, 2004
We consider the problem of finding positive solutions of ∆u + λu + u q = 0 in a bounded, smooth d... more We consider the problem of finding positive solutions of ∆u + λu + u q = 0 in a bounded, smooth domain Ω in R 3 , under zero Dirichlet boundary conditions. Here q is a number close to the critical exponent 5 and 0 < λ < λ1. We analyze the role of Green's function of ∆+λ in the presence of solutions exhibiting single and multiple bubbling behavior at one point of the domain when either q or λ are regarded as parameters. As a special case of our results, we find that if λ * < λ < λ1, where λ * is the Brezis-Nirenberg number, i.e. the smallest value of λ for which least energy solutions for q = 5 exist, then this problem is solvable if q > 5 and q − 5 is sufficiently small.
Journal de Mathématiques Pures et Appliquées, 2002
In this paper, we nd optimal constants of a special class of Gagliardo-Nirenberg type inequalitie... more In this paper, we nd optimal constants of a special class of Gagliardo-Nirenberg type inequalities which turns out to interpolate between the classical Sobolev inequality and the Gross logarithmic Sobolev inequality. These inequalities provide an optimal decay rate (measured by entropy methods) of the intermediate asymptotics of solutions to nonlinear di usion equations.
Indiana University Mathematics Journal, 1998
ABSTRACT It is well known that every non-trivial solution of u t =Δu m +u m in ℝ N ×[0,∞), u(x,0)... more ABSTRACT It is well known that every non-trivial solution of u t =Δu m +u m in ℝ N ×[0,∞), u(x,0)=u 0 (x)≥0 on ℝ N , with m&gt;1, blows up in finite time. We study the blow-up set and the blow-up profile of a solution u(x,t) to this equation with blow-up time T&gt;0, under the assumption that u 0 (x) is compactly supported. We prove that, up to subsequences, (T-t) 1/(m-1) u(x,t) converges as t→T to w(x). Here w(x) is a finite sum of translations with disjoint supports of the unique positive radially symmetric, compactly supported, solution of Δw m +w m -w/(m-1)=0. The centers of these supports do not go beyond the smallest ball containing the support of u 0 and, u(x,t) remains uniformly bounded away from these supports. An estimate of the blow-up time is also provided.
Indiana University Mathematics Journal, 2001
Indiana University Mathematics Journal, 1999
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Papers by Manuel M Sánchez del Pino
not my papers by Manuel M Sánchez del Pino