个人简介

2004 Visiting Professor, Unité de Bioinformatique Structurale, Institut Pasteur, Paris, France 2003–present Member, Cambridge Collaborative Computation NMR (CCPN), UK 2003 Visiting Professor, Department of Biochemistry, Cambridge University, UK 1992 Visiting Professor, Department of Organic Chemistry, University of Barcelona, Spain 1990 Visiting Professor, Macromolecular Chemistry Unit, Catalonia Polytechnic University, Barcelona, Spain 1989 Visiting Professor, Department of Chemistry, University of Utrecht, The Netherlands 1988–present Professor, Carnegie Mellon University 1976–1988 Associate Professor, Carnegie Mellon University 1974–1976 Assistant, Institut für Molekularbiologie und Biophysik, Swiss Federal Institute of Technology, Switzerland 1973 Lecturer, University of California, Berkeley 1971–1974 Postdoctoral Research Associate, University of California, Berkeley 1971 Ph.D. Biophysics, University of California, Berkeley 1963 Licentiate in Physics, Cordoba National University, Argentina

研究领域

Biophysical

We exploit high-field NMR spectroscopy to elucidate the conformation of peptides and proteins in solution. A main emphasis of our effort is in deriving structures compatible with NMR constraints, such as experimental Overhauser connectivities, via interproton dipolar interactions, relaxation matrix analysis, distance-geometry computations and energy minimization/molecular dynamics simulations. The structures thus generated are analyzed vis-a-vis reported mutagenesis studies and compared with available X-ray crystallographic models. The dynamic behavior of the protein is experimentally characterized by means of magnetic relaxation, hydrogen isotope exchange and thermal stability profiles. These data, in turn, are correlated with the theoretical models, which thus provide valuable criteria for unveiling flexible regions of the polypeptide fold and to further refine the structure. The long-term goal of our project is to understand the biological function of proteins under physiological conditions, including accurate analysis of ligand-binding properties. This way, we hope to provide reliable criteria for tailored drug-protein interaction design. A main share of our effort focuses on domain substructures of blood coagulation proteins, the plasminogen system in particular. We are also investigating protein modules within cell matrix metalloproteinases, and proteins related to neurological function in the context of evolutionary relatedness. Another thrust of our effort is to develop robust algorithms for fast-throughput protein structural characterization requiring minimal NMR data.

近期论文

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M.D. Battistel, A. Grishaev, S.S.A. An, F.J. Castellino & M. Llinás (2009). "Solution Structure and Functional Characterization of Human Plasminogen Kringle 5". Biochemistry 48, 10208-10219. M.T. Christen, P. Frank, J. Schaller & M. Llinás (2010). "Human Plasminogen Kringle 3: Solution Structure, Functional Insights, Phylogenetic Landscape". Biochemistry 49, 7131-7150. H.J. Kim, M.Y. Choi, H.J. Kim & M. Llinás (2010). "Conformational Dynamics and Ligand Binding in the Multi-Domain Protein PDC109". PLoS ONE 5(2): e9180. doi:10.1371/journal.pone.0009180 .G.A. Bermejo & M. Llinás (2010). "Structure-Oriented Methods for Protein NMR Data Analysis". Progr. NMR Spectroscopy 56, 311-328. M.T. Christen (2010), Doctoral Dissertation, Carnegie Mellon University. G.A. Bermejo & M. Llinás (2008). "Deuterated Protein Folds Obtained Directly from Unassigned Nuclear Overhauser Effect Data". J. Am. Chem. Soc. 130, 3797-3805 A. Grishaev & M. Llinás (2005). “Protein Structure Elucidation from Minimal NMR Data: the CLOUDS Approach”Meth. Enzymology 394, 261-295. ABACUS, a Direct Method for Protein NMR Structure Computation via Assembly of Fragments A. Grishaev1, C. A. Steren1, A. Pineda-Lucena2, C. Arrowsmith2 & M. Llinás1* (submitted) Grishaev A, Llinas M. BACUS: A Bayesian protocol for the identification of protein NOESY spectra via unassigned spin systems(*). J Biomol NMR. 2004 Jan;28(1):1-10. Grishaev A, Llinas M. Sorting signals from protein NMR spectra: SPI, a Bayesian protocol for uncovering spin systems. J Biomol NMR. 2002 Nov;24(3):203-13. J.T. Douglas, P.D. von Haller, M. Gehrmann, M. Llinás & J. Schaller (2002). "The two-domain NK1 fragment of plasminogen: folding, ligand binding, and thermal stability profile". Biochemistry (in the press). M. Gehrmann, K. Briknarová, L. Bányai, L. Patthy & M. Llinás (2002) "The col-1 module of human matrix metalloproteinase-2 (MMP-2): structural/functional relatedness between gelatin-binding fibronectin type II modules and lysine-binding kringle domains". Biol. Chem. 383, 137-148. L. Örning, , P.M. Fischer, C.-K. Hu, E. Agner, M. Engebretsen, M. Husbyn, L.B. Petersen, U. Ørvim, M. Llinás, & K. Sakariassen (2002) "A cyclic pentapeptide derived from the second EGF-like domain of factor VII is an inhibitor of tissue factor dependent coagulation and thrombus formation" Thrombosis and Haemostasis 87, 13-21. V.O. Lewis, M.S. O'Reilly, M. Gehrmann, M. Llinás, J. Schaller, & L. Weissbach (2001). "Inhibition of Tumor Growth by Plasminogen-Related Protein B." Anticancer Res. 21, 2287-2291. O.A. Ozhogina, M. Trexler, L. Bányai, M. Llinás & L. Patthy (2001) "Origin of fibronectin type II (FN2) modules: Structural analyses of distantly-related members of the kringle-family identify the kringle-domain of neurotrypsin as a potential link between FN2 domains and kringles." Protein Sc. 10, 2114-2122. K. Briknarová, M. Gehrmann, L. Bányai, H. Tordai, L. Patthy & M. Llinás (2001) "Gelatin Binding Region of Human Matrix Metalloproteinase 2: Solution Structure, Dynamics and Function of the Col-23 Two-Domain Construct." J. Biol. Chem. 276, 27613-27621. K. Briknarová, S. Takayama, L. Brive, M.L. Havert, D.A. Knee, J.Velasco, S. Homma, E. Cabezas, J. Stuart, D.W. Hoyt, A.C. Satterthwait, M. Llinás, J.C. Reed & K.R. Ely (2001). "Structural Analysis of BAG1 Cochaperone and its Interactions with Hsc70 Heat Shock Protein." Nature Struct. Biol. 8, 349-352. C.-K. Hu, E. Agner, L. Örning, K.S. Sakariassen, R.W. Stephens, M. Llinás & P.M. Fischer (2001) "Synthesis, Biological Activity, and Solution Structures of a Cyclic Dodecapeptide from the EGF2-Domain of Blood Coagulation Factor VII." J. Peptide Res. 57, 462-472 . D.N. Marti, J. Schaller & M. Llinás (1999) "Solution Structure and Dynamics of the Plasminogen Kringle 2-AMCHA Complex: 31-Helix in Homologous Domains." Biochemistry 38, 15741-15755. K. Briknarová, A. Grishaev, L. Bányai, H. Tordai, L. Patthy & M. Llinás (1999) "The Second type II Module from Human Matrix Metalloproteinase 2: Structure, Function and Dynamics" Structure 7, 1235-1245.