Structure, folding and design of integral membrane proteins

What is the biophysical basis of transmembrane helix-helix interaction?

We are interested in investigating this process and in developing methods for predicting and designing oligomeric complexes of transmembrane helices.

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News
October 13, 2017

New publication: Cα-H···O=C hydrogen bonds contribute to stabilize the GASright motif

Congratulations to Samantha Anderson, Ben Mueller, and Evan Lange for the publication of their latest paper in JACS! They combined the power of computation and experimentation to analyze the forces that drive the association of an array of transmembrane dimers belonging to the common GASright structural motif. They found that hydrogen bonds in which the donor are Cα-H carbons, combined with van der Waals packing predict the stability of these GxxxG-mediated dimers in biological membranes. The finding provides experimental evidence that weak hydrogen bonds can drive the association of transmembrane helices.

  • Anderson SM*, Mueller BJ*, Lange EJ, Senes A. "A combination of Cα-H hydrogen bonds and van der Waals packing modulates the stability of GxxxG-mediated dimers in membranes" J Am Chem Soc. 2017 In press doi: 10.1021/jacs.7b07505 (*authors contributed equally)
July 18, 2017

Congratulations and good luck Deena!

Deena has graduated with a Master's degree. During her time in the lab, Deena performed in vivo studies on the E. coli bacterial divisome proteins FtsB and FtsL. Deena is moving to the Massachusetts Institute of Technology to work in Laura Kiessling's lab.

July 18, 2017

Good luck, Claire!

After three years as a undergraduate and two years as a lab intern, Claire Armstrong is moving to the University of Colorado at Boulder for graduate school.

April 3, 2017

Congratulations to our three Sams for earning fellowships!

Congratulations to fellowship recepients in the lab: graduate students Sam Anderson and Sam Craven were awarded the Dr. James Chieh-Hsia Mao Wisconsin Distinguished Graduate Fellowship, and Sam Condon the William R. & Dorothy E. Sullivan Wisconsin Distinguished Graduate Fellowship, for the 2017-18 academic year.

March 13, 2017

Sam Anderson is awarded a CIBM Predoctoral Traineeship

Sam is awarded a tranineeship with the Computation and Informatics in Biology and Medicine training program. Sam is the third Senes lab graduate student in the lab to be selected for the training grant, after Ben Mueller and Sam Condon. Her project focuses on high-throughput computational and experimental analysis of the GASright motif.

January 10, 2017

New publication: Ptc7p dephosphorylates select mitochondrial proteins to enhance metabolic function

Congratulations to Samson Condon for the publication of his latest paper in Cell Reports! Sam collaborated with Pagliarini and Coon groups and helped modeling the mechamism by which phosphorilatin regulates the activity of the mitochondrial phosphatase Prc7p.

  • Guo X, Niemi NM, Hutchins PD, Condon SGF, Jochem A, Ulbrich A, Higbee AJ, Russell JD, Senes A, Coon JJ, and Pagliarini DJ. "Ptc7p dephosphorylates select mitochondrial proteins to enhance metabolic function Cell Reports 2017 18, 307-13 [PDF]
July 19, 2016

New publication: A high-throughput variant of the TOXCAT assay

Congratulations to Claire Armstrong for the publication of her first paper in Biochim. Biophys. Acta! She developed an asay that can help us determine association strength faster and more consistently than TOXCAT.

  • Armstrong CR and Senes A "Screening for transmembrane association in divisome proteins using TOXGREEN, a high-throughput variant of the TOXCAT assay Biochim. Biophys. Acta 2016 1858, 2573-83 [PDF]
April 20, 2016

New publication: Review article on computational design of membrane proteins

Alessandro publishes a review article in Nature Structural and Molecular Biology on the progress of the field of membrane protein design, in collaboration with his friend Patrick Barth (Baylor College of Medicine).

  • Barth P, Senes A "Toward high-resolution computational design of the structure and function of helical membrane proteins" Nat Struct Mol Biol 2016 23, 475-80 [PDF]
April 7, 2016

Congratulations fellowship recepients!

Congratulations to several fellowship recepients in the lab: graduate student Sam Anderson for being awarded the Dr. James Chieh-Hsia Mao Wisconsin Distinguished Graduate Fellowship for the 2016-17 academic year; graduate student Deena Mahbuba for being awarded the Steenbock Predoctoral Fellowship for the 2016-17 academic year; and undergraduate student Lucy Jiang for having been awarded a Biochemistry Undergraduate Summer Research Scholarship.

February 12, 2016

Good luck, Rika!

After sticking around for one more year as a postdoc in the lab, former graduate student Rika Khadria is moving to the University of North Carolina at Chapel Hill to be a postdoc in the lab of Mike Ramsey.

February 1, 2016

New postdoc Elizabeth Caselle joins the lab

The Senes lab welcomes Beth, who just received a PhD in Chemistry from joined from Syracuse University, where she worked in the Korendovych lab.

December 23, 2015

New publication: BH3-in-groove dimerization initiates and helix 9 dimerization expands Bax pore assembly in membranes

Congratulations to Sabareesh Subramaniam and Samson Condon for the publication of their latest paper in EMBO J! They collaborated with the Lin lab at the University of Oklahoma to predict how conformational changes mediate pore assembly for the apoptotic regulator Bax.

  • Zhang Z, Subramaniam S, Kale J, Liao C, Huang B, Brahmbhatt H, Condon SGF, Lapolla SM, Hays, FA, Ding J, He F, Zhang XC, Li J, Senes A, Andrews DW, Lin J. "BH3-in-groove dimerization initiates and helix 9 dimerization expands Bax pore assembly in membranes EMBO J 2016 35, 208-36 [PDF]
May 13, 2015

New publication: Review article on FRET for transmembrane helices

Congratulations to Rika Khadria for the publication of her latest review in Biopolymers! She discusses the various factors that contribute to performing effective FRET with transmembrane helices.

  • Khadria AS and Senes A "Fluorophores, environments and quantification techniques in the analysis of transmembrane helix interaction using FRET" Biopolymers 2015 104, 247-264 [PDF]
May 11, 2015

Dr. Ben!

Congratulations to Ben Mueller for successfully defending his PhD thesis in Biochemistry.

During his thesis, Ben has been studying an important transmembrane interaction motif using computational and experimental methods. He has also designed an algorithm that can predict transmembrane dimers from sequence alone. He has published three articles, with two more currently in preparation for submission.

Ben will move to the lab of Jens Meiler at Vanderbilt University at the end of the summer.

April 23, 2015

Congratulations fellowship recepients!

Congratulations to several fellowship recepients in the lab: graduate student Sam Craven for being awarded the Willaim H. Peterson Fellowship for the 2015-16 academic year; undergraduate student Evan Lange for having received a 2015-16 Wisconsin Hilldale Undegraduate/Facutly Reserach Fellowship; and undergraduate student Praisten Tiano for having been awarded a Biochemistry Undergraduate Summer Research Scholarship.

December 15, 2014

Three new PhD students join the lab!

The Senes lab welcomes Gladys Díaz-Vázquez (Biophysics program) and Sam Anderson and Deena Mahbuba (Biochemistry) who just joined!

December 1, 2014

Dr. Loren!

Congratulations to Loren LaPointe for successfully defending her PhD thesis in Biochemistry.

During her time in the lab, Loren has studied the structural organization of the complex formed by two essential proteins of the bacterial divisome, FtsB and FtsL. She has already published 3 papers, and more are likely to come. She will soon move to Tennessee to continue to work on membrane proteins, as a postdoc in the structural biology lab of Chuck Sanders at Vanderbilt University.

November 24, 2014

Dr. Rika!

Congratulations to Rika Khadria for successfully defending her PhD thesis in Biochemistry.

During her time in the lab, Rika has used FRET as a tool for understanding the association of membrane protein complexes. She has already published 4 papers, 3 of which are first author. Rika will stay in the lab for another year to continue single-molecule studies of the FtsB-FtsL complex in collaboration with Aaron Hoskins.

September 15, 2014

New publication: CATM prediction and experimental validation of a mitochondrial TM domain

Congratulations to Rika Khadria and Ben Mueller for the publication of their latest paper in JACS! In collaboration with Jon Stefely and Dave Pagliarini, they determined that the TM domain of the mitochondrial kinase ADCK3 self-associates, forming a GASright motif using an extended Gly-rich interface.

  • Khadria AS, Mueller BK, Stefely JA, Tan CH, Pagliarini DJ and Senes A "A Gly-zipper motif mediates homo-dimerization of the transmembrane domain of the mitochondrial kinase ADCK3" J Am Chem Soc 2014 136, 14068-77 [PDF]
September 3, 2014

New publication: A new backbone-dependent energy library

Congratulations to Sabareesh Subramaniam for the publication of his latest paper, an improved version of his previous energy-based conformer library for side chain modeling.

  • Subramaniam S and Senes A and "Backbone dependency further improves side chain prediction efficiency in the Energy-Based Conformer Library (bEBL)" Proteins 2014 81 (11), 3177-3187 [PDF]
July 1, 2014

Alessandro is promoted to Associate Professor

A major milestone for the lab was reached today, as Alessandro was promoted to Associate Professor with tenure!

March 13, 2014

Sam Condon is awarded a CIBM Predoctoral Traineeship

Sam is awarded a tranineeship with the Computation and Informatics in Biology and Medicine program. His project focuses on the computational and experimental analysis of desease causing mutation in membrane proteins from large scale data sets.

February 19, 2014

Dr. Sab!

Congratulations to Sabareesh Subramaniam for successfully defending his PhD thesis in Computational Biology.

During his time in the lab, Sab has published 5 papers, 3 of which are first author. Another first-author paper is currently under review and more are likely to come. Sab now works at VMware in Silicon Valley.

January 28, 2014

New publication: The fold of the Glycophorin A transmembrane dimer is optimized for formation of Cα-H hydrogen bonds

Congratulations to Ben Mueller and Sabareesh Subramaniam for the publication of their latest paper in PNAS! They demonstrated that a common motif for helix-helix interaction in membrane proteins is optimized for the formation of hydrogen bonds in which the donor is a carbon.

  • Mueller BK*, Subramaniam S* and Senes A "A frequent, GxxxG-mediated, transmembrane association motif is optimized for the formation of interhelical Cα-H hydrogen bonds" Proc Natl Acad Sci USA 2014 111(10) E888-95 (*authors contributed equally) [PDF]
November 21, 2013

Rika wins Science Magazine "Dance your PhD" prize

Congratulations to Rika Khadria for winning the first prize in Chemistry at the Dance your PhD competition, with an interpretative dance of her thesis project.

Find her video here.

Alessandro Senes
Associate Professor
Department of Biochemistry - UW-Madison
433 Backcock Dr., Room 419
Madison, WI 53706
office (+1) 608-890-2584
lab. (+1) 608-262-7355