www.raul-padron.org - raul-padron.no-ip.org - raul-padron.kissr.com Last updated: September 7, 2018
Padrón lab
Rakesh Rocky ant
Superb photograp "The Ants Dreams!" by Rakesh Rocky   @rakeshrocky1705

Raúl Padrón

Dr. Raúl Padrón, Ph. Sc. in Physiology and Biophysics of IVIC (1979), is Senior Emeritus Investigator at the Center of Structural Biology (CBE) of the Venezuelan Institute for Scientific Research (IVIC) in Caracas, Venezuela, where he started his scientifc career as visiting student in 1966. After his postdoctoral work with Hugh E. Huxley at the MRC Laboratory of Molecular Biology (Cambridge, UK) (supported by the Alberto Vollmer Foundation)  he founded the Deparment of Structural Biology of IVIC in 1997, where he was an International Research Scholar of the Howard Hughes Medical Institute (HHMI) from 1997 until 2011. He has devoted his career to the study of the structure and function of the myosin thick filaments of skeletal, cardiac and smooth muscle and the myosin interacting-head motif (IHM) structure and function, with their implications on the muscle relaxed state, super-relaxation, thick filament activation and human muscle diseases like hypertrophic and dilated cardiomyopathy. His honors includes: Polar Prize ("Lorenzo Mendoza Fleury" Prize) (1991) of Fundación Empresas Polar (FEP); CONICIT Biology Prizes (1989, 1990, 1996); FONACIT Biology Prize (2005); and the National Prize in Science and Technology of Venezuela (2008). He is an elected member of the Latin-American Academy of Sciences (ACAL) (2002), and The World Academy of Sciences (TWAS) (2004),  and an elected foreign associate of the National Academy of Sciences of the U.S.A (2018).

Center of Structural Biology (CBE) "Humberto Fernández-Morán" - Venezuelan Institute for Scientific Research (IVIC)
CBE is a node of the Centro de Biología Estructural del Mercosur (CeBEM), houses the Centro Latino-Américano FEI de Crio-Microscopía Electrónica (CLAFCME)
and was founded in honor of Humberto Fernández-Morán, the cryo-EM pioneer.
Read (in Spanish) how the Center of Structural Biology "Humberto Fernández-Morán was created
      Micro radial RCR 750 : "Raúl Padrón y sus tarántulas"  de  Micros radiales ACFIMAN        
  Contact: Centro de Biología Estructural "Humberto Fernández-Morán", IVIC, APDO 20632, Caracas 1020A, Venezuela. (map)  Phone:+58-212-504-1435/1717/1434 (sec/adm) Fax:-1444 
Twitter: @raulpadron      LinkedIn: raulpadron      Facebook: padronraul       Instagram: padronraul        E-mail: Raul Padron´s email address 

Future plans - October 2018-2022: single-particle cryo_EM


Supramolecular Structure Laboratory´s  muscle team - IVIC´s Center of Structural Biology
Three generations on muscle physiology and structure at I.V.I.C.
Gustavo Márquez, Lorenzo Alamo, Raúl Padrón, Antonio Pinto and sebastian Duno
Raúl Padrón, Sebastian Duno & Carlo Caputo - February 2, 2018
Dr. Gustavo  Márquez, Lic. Lorenzo Alamo, Dr. Raúl Padrón, Electronic Engineer. Antonio Pinto  and Lic Sebastian Duno
Dr. Raúl Padrón, Lic. Sebastian Duno and Dr. Carlo Caputo
Instituto de Biología Experimental, UCV, Caracas, Venezuela - February 2, 2018 (Photograph credit: Dr. Pura Bolaños)

Padrón lab people
Structural Biology Laboratory 2018
Blue tarantula
From right to left:   Sebastian Duno, Ruth García, Gustavo Márquez, Pura Bolaños (CBB) , Antonio Pinto, Lorenzo Alamo and Raúl Padrón.   June 2018
Blue tarantula
Current members: 
Retired Research Associates (working ad honorem): 
Electronic Eng. Antonio Pinto EE, Lic. Biology Lorenzo  Alamo
Research associates:
Dr. Gustavo Márquez, M. Sc. Ruth García,  Lic. Biol.  Sebastián Duno
Former members:
Associated Investigators: Dr. Guidenn Sulbarán (Now in France)
Former research Associates:
Dr. Jose Reinaldo Guerrero (Retired), M. Sc. Maristela Granados, Eng. Franklin Méndez (Now in Colombia), Dr. Aivett Bilbao (Now in U.S.A.), M. Sc. Galax Joya (Now in Chile)
Postdoctoral Fellows: Dr. Carlos Hidalgo 1997-2000 (Now in U.S.A.),  Dr. Rosalba Rodriguez 2009-2012 (Now at IVIC-CBE),  Dr. Guidenn Sulbáran 2009-2012 (France 20-2-2016),  Dr. Lucía Proietti d´Speratti (Now in U.S.A. 1-2-2016)
Ph. D Graduates:
Dr. Jose Reinaldo Guerrero 1995, Dr. Julio Ortiz 2002 (Now in France),  Dr. María Elena Zoghbi 2003 (Now in U.S.A.), Dr. Reicy Brito 2010 (Now in Spain).
M. Sc. Graduates,: 
Dr. Nelly Panté 1986 (Now in Canada),  Dr. José Reinaldo Guerrero 1989,  M. Sc. Maristela Granados 1993,  M. Sc. Karina Temperini 2001 (Argentina, now in Argentina),  M. Sc. Nelitza  Linarez 2001,  Dr. Antonio Biasutto 2011- (Now in U.K.).
Lic. Biology graduates:
Dr.Hernando Sosa 1986 (Now in U.S.A.),  Lic. Patricia Valero 1991, Lic. Jackeline Rodriguez 1991 
B. Sc. Graduates:
Dr. Claire L. Riggs 2010 (U.S.A., now in U.S.A.)
Lab visitors
Dr.Robert Perz-Edwards  1991-1992 (U.S.A., now in U.S.A.),  Leroy Lindsay MD 2005 (U.S.A., now in Spain),  Mina-Han Tran 2008/2009 (U.S.A., now in U.S.A.)
Academic tree    Tree
Padron lab latest publications

L. Alamo, A. Pinto, G. Sulbarán,  J.  Mavárez & R. Padrón “Lessons from a tarantula: New insights into myosin interacting-heads motif evolution and its implications on disease”  Biophys. Rev https://doi.org/10.1007/s12551-017-0292-4.

Mendoza, F. & Padrón, R. La Revolución de la Resolución: la Crio-Microscopía Electrónica de partículas aisladas resuelve la estructura atómica de biomoléculas en solución. Avances en Química: 13 (1) 7-13, 2018.    PDF
Lee K H, Sulbarán G,  Yang S, Mun J Y, Alamo L, Pinto A, Sato O, Ikebe M, Liu X, Korn E D, Sarsoza F, Bernstein S I, Padrón R, Craig R (2018) Interacting-heads motif has been conserved as a mechanism of myosin II inhibition since before the origin of animals. Proc Natl Acad Sci USA 115:E1991-E2000 https://doi.org/10.1073/pnas.1715247115 PDF SI PDF
L.  Alamo, N. Koubassova, A. Pinto, R. Gillilan,  A. Tsaturyan & R. Padrón  2017  Lessons from a tarantula: New insights into muscle thick filament and myosin interacting-heads motif structure and function Biophys. Rev. 9:461-480  DOI 10.1007/s2551-017-0295-4 SharEdit PDF:  http://rdcu.be/vz7T
L. Alamo, J. S. Ware, A. Pinto, R. E. Gillilan, J. G. Seidman, C. E. Seidman & Raúl Padrón 2017 Effects of myosin variants on interacting-heads motif explain distinct  hypertrophic and dilated cardiomyopathy phenotypes eLife 2017;6:e24634 doi: 10.7554/eLife.24634  PDF   SI PDF
Padron lab four questions
Myosin II thick filament structure, function, evolution and disease
Myosin II interacting-heads motif (IHM) structure, function, evolution and disease
Whis is the structure of relaxed thick filaments?  Which is the structure of the switched OFF IHM?
How the relaxed thik filament structure is conserved?
How the relaxed IHM structure is conserved?
How thick filaments are relaxed and activated? How the IHM is relaxed and activated?
How thick filaments malfunction on disease?
How IHM malfunction on disease?
Padrón lab achievements

2 nm resolution three-dimensional reconstruction of  tarantula striated muscle thick filament

Which is the structure of relaxed tarantula thick filaments
Structural evidences of the tarantula thcik filament
Low-angle X-ray diffraction patterns of relaxed tarantula relaxed muscle
Electron micrographs of relaxed isolated tarantula thick filaments
Structural evidences of the tarantula thick filament backbone
http://www.raul-padron.org/lab/Fig_%20I-2.png http://www.raul-padron.org/lab/Fig_I-3.png
The search for the tarantula thick filament structure:
from 5.0 to 1.3 nm resolution (1985-2016)

Quasi-atomic model of the tarantula thick filament and the tarantula IHM PDB 3JBH quasi-atomic model
DOI 10.1007/s2551-017-0295-4   http://rdcu.be/vz7T

(a,b) Tarantula thick filament 3D-reconstruction, (a) IHM quasi-atomic model PDB 3JBH, (c) myosin II quasi-atomic model and (d) thick filament quasi-atomic model
Tarantula low-angle X-ray diffraction pattern (a) vs. diffraction of the tarantula quasi-atromic model (b,c)
http://www.raul-padron.org/lab/Fig_I-6.png http://www.raul-padron.org/lab/Fig_I-7.png
IHM´s Intramolecular and intermolecular interactions
(Alamo et al. J. Mol. Biol. 2016)
DOI 10.1007/s2551-017-0295-4   http://rdcu.be/vz7T
Myosin II Interacting-Heads Motif (IHM) quasi-atomic models

myosin II
Alamo et al. J. Mol. Biol. 2008
myosin II
Alamo et al. J. Mol. Biol. 2016
myosin II
Alamo et al. eLife 2017
RCSB Protein Data Bank RCSB Protein Data Bank RCSB Protein Data Bank
Protein Data Bank in Europe Protein Data Bank in Europe Protein Data Bank in Europe
EMD-1950 EMD-1950 EMD-2240
20 A 20 A 28 A
Schistosome Mansoni myosin II IHM PDF 3JAX RCSB Protein Data Bank  RCSB NGL Viewer  Protein Data Bank in Europe   Yorodumi PDB/EMDB/SASBD  EMD-6370  23 A
Tarantula myosin II and paramyosin sequences
Myosin II heavy chain (MHC)
Myosin regulatory light chain (RLC) Myosin essential light chain (ELC)
Paramyosin heavy chain (PM)
GenBank: KT619079.1
Alamo et al. J. Mol. Biol. 2016
GenBank: KT390186.1
Zhu et al. 2009
GenBank: EU090070.1
Alamo et al. J. Mol. Biol. 2008
GenBank: KT390185.1
Zhu et al. 2009
GenBank: KT692662.1
Alamo et al. J. Mol. Biol. 2016

How the relaxed thik filament structure is conserved?
How the relaxed IHM structure is conserved?

How thick filaments and IHMs are relaxed and activated?

Swaying heads, potentiation and postetanic potentiation mechanisms
Alamo et al. J. Mol. Biol. 2008, Brito et al. J. Mol. Biol. 2011
The cooperative phosphorylation activation (CPA) mechanism of thick filament activation
Sulbarán et al. Biophys. J. 2011, Espinoza-Fonseca et al. Mol. BioSyst. 2015, Alamo et al. Mol. BioSyst. 2015Alamo et al. Biophys. Rev. 2017, Biasutto et al. in preparation
The swaying-swinging, tilting crosbridge-sliding filament mechanism
Alamo et al. Biophys. Rev.2017
How thick filaments malfunction on disease?
IHM implications on hypertrophic (HCM) and dilated (DCM) cardiomyopathy
Effects of myosin variants on interacting-heads motif (IHM) explain distinct hypertrophic (HCM) and dilated (DCM) cardiomyopathy phenotypes
Lorenzo Alamo, James S. Ware, Antonio Pinto, Richard E. Gillilan, Jonathan G. Seidman, Christine E. Seidman & Raúl Padrón  eLife 2017;6:e24634 doi: 10.7554/eLife.24634
Padron lab Alamo et al. 2017 Fig. 1
Cardiac β-myosin variants cause hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM) by disrupting sarcomere contraction and relaxation.  The locations of variants on isolated myosin head structures predict contractility effects but not the prominent relaxation and energetic deficits that characterize HCM. During relaxation, pairs of myosins form interacting-heads motif (IHM) structures that with other sarcomere proteins establish an energy-saving, super-relaxed (SRX) state.  Using a human β-cardiac myosin IHM quasi-atomic model (PDB 5TBY), we defined interactions sites between adjacent myosin heads and associated protein partners, and then analyzed rare variants from 6112 HCM and 1315 DCM patients and 33,370 ExAC controls. HCM variants, 72% that changed electrostatic charges, disproportionately altered IHM interaction residues (expected 23%; HCM 54%, p=2.6×10−19; DCM 26%, p=0.66; controls 20%, p=0.23).  HCM variant locations predict impaired IHM formation and stability, and attenuation of the SRX state - accounting  for altered contractrility, reduced diastolic relaxation, and increased energy consumption, that fully characterize HCM pathogenesis.

MRC London Institute of Medical Sciences  Biomedical picture of the day  "Spinning spider proteins" by Deborah Oakley
Que hacen los académicos (ACAL)
Christine E. Seidman´s lecture "Hearts, Spiders, and Relaxation: Voyages in Hypertrophic Cardiomyopathy" NHLBI 70th Anniversay - April 25, 2018
Micro radial RCR 750 : "Raúl Padrón y sus tarántulas"  de  Micros radiales ACFIMAN
Padrón lab journal covers

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Webmaster: Raúl Padrón - September 7, 2018