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Peter H. von Hippel

Peter H. von Hippel

Emeritus, Chemistry and Biochemistry
Member, IMB

Ph.D., Massachusetts Institute of Technology
M.S., Massachusetts Institute of Technology
B.A., Massachusetts Institute of Technology

Office: Klamath Hall Room 215A
Office Phone: 541-346-6097
Lab: Klamath Hall Room 205
Lab Phone: 541-346-4212

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Research Interests

Professor von Hippel is retired from teaching, but continues to run fully active and funded research program(s). Applications from potential postdoctoral fellows and undergraduate research participants are welcome.

My associates and I are using physical biochemical approaches to study what might be called the molecular basis of gene expression. Most of our experimental work is concerned with the function and regulation of the complexes that control DNA transcription and replication, with studies focused primarily on transcription with the E. coli DNA-dependent RNA polymerase and its regulatory factors and on replication with the seven-protein bacteriophage T4-coded DNA replication system. Comparative studies are also underway using selected components of some equivalent eukaryotic systems.

In transcription our group is studying the transcription cycle, both at the overall operon level and at the level of the various steps of the single-nucleotide addition-excision cycle. At the operon level we are studying regulatory interactions that control activation and repression at initiation, the kinetics of elongation, and the molecular bases of the elongation-termination decision at both intrinsic and rho-dependent transcription terminators, together with the mechanisms of action antitermination factors. We have recently completed a study of E. coli transcription termination factor rho, in terms of its function as a specific RNA-DNA helicase and as a transcript terminator. Our antitermination studies have focussed on the mechanisms of action of the N protein of phage lambda in N-dependent antitermination systems. At the single-nucleotide addition-excision cycle level we are using various kinetic techniques to understand the molecular origins of transcriptional processivity and fidelity.

In replication our work began with studies of the cooperative binding of the T4 gene 32 (single-stranded DNA binding) protein to the single-stranded DNA (and RNA). This then led us to examine the interactions of the other components of the system, including those of the DNA polymerase with the primer-template and the polymerase accessory proteins. These studies have shown that the basically nonprocessive T4 DNA polymerase can be rendered fully processive by means of "sliding-clamp" processivity factor, and that the role of the other accessory proteins is to carry out the specific and ATP-dependent loading of the processivity factor onto the polymerase at the primer-template junction in the replication fork. The resulting complex can carry out leading strand DNA replication with essentially in vivo rate, fidelity, and processivity. The helicase of the T4 DNA replication system functions as a hexamer and, in combination with a single T4 primase subunit, forms a stable primosome subassembly. We have recently also shown a direct coupling between the polymerase and the helicase. This complex alone, if properly loaded onto a model replication fork, can carry out processive synthesis on a double-stranded DNA construct at the physiological rate. The mode of assembly of these components into a fully functional and coupled DNA replication system is currently being studied.

In all these studies we emphasize the elucidation of the detailed mechanisms and general principles of protein-nucleic acid and protein-protein interactions that underlie the function of these biologically central complexes. Over the last few years, in collaboration with the laboratory of Andrew Marcus, we have developed new spectroscopic and single-molecule biophysical approaches to studying the mechanisms and dynamics of various components of the above replication and transcription systems. For details, see recent publications, and also the website of IMB Associate Member Andrew Marcus.

Recent publications

(pulled from pubmed)

Recent publications

(pulled from pubmed)

John Schellman and the birth of protein folding.
Baldwin RL, von Hippel PH
Proc Natl Acad Sci U S A 2015 Jun 2;112(22):6776-7
A multilaboratory comparison of calibration accuracy and the performance of external references in analytical ultracentrifugation.
Zhao H, Ghirlando R, Alfonso C, Arisaka F, Attali I, Bain DL, Bakhtina MM, Becker DF, Bedwell GJ, Bekdemir A, Besong TM, Birck C, Brautigam CA, Brennerman W, Byron O, Bzowska A, Chaires JB, Chaton CT, Cölfen H, Connaghan KD, Crowley KA, Curth U, Daviter T, Dean WL, Díez AI, Ebel C, Eckert DM, Eisele LE, Eisenstein E, England P, Escalante C, Fagan JA, Fairman R, Finn RM, Fischle W, de la Torre JG, Gor J, Gustafsson H, Hall D, Harding SE, Cifre JG, Herr AB, Howell EE, Isaac RS, Jao SC, Jose D, Kim SJ, Kokona B, Kornblatt JA, Kosek D, Krayukhina E, Krzizike D, Kusznir EA, Kwon H, Larson A, Laue TM, Le Roy A, Leech AP, Lilie H, Luger K, Luque-Ortega JR, Ma J, May CA, Maynard EL, Modrak-Wojcik A, Mok YF, Mücke N, Nagel-Steger L, Narlikar GJ, Noda M, Nourse A, Obsil T, Park CK, Park JK, Pawelek PD, Perdue EE, Perkins SJ, Perugini MA, Peterson CL, Peverelli MG, Piszczek G, Prag G, Prevelige PE, Raynal BD, Rezabkova L, Richter K, Ringel AE, Rosenberg R, Rowe AJ, Rufer AC, Scott DJ, Seravalli JG, Solovyova AS, Song R, Staunton D, Stoddard C, Stott K, Strauss HM, Streicher WW, Sumida JP, Swygert SG, Szczepanowski RH, Tessmer I, Toth RT 4th, Tripathy A, Uchiyama S, Uebel SF, Unzai S, Gruber AV, von Hippel PH, Wandrey C, Wang SH, Weitzel SE, Wielgus-Kutrowska B, Wolberger C, Wolff M, Wright E, Wu YS, Wubben JM, Schuck P
PLoS One 2015;10(5):e0126420
Increased subtlety of transcription factor binding increases complexity of genome regulation.
von Hippel PH
Proc Natl Acad Sci U S A 2014 Dec 9;111(49):17344-5
Electronic transition moments of 6-methyl isoxanthopterin--a fluorescent analogue of the nucleic acid base guanine.
Widom JR, Rappoport D, Perdomo-Ortiz A, Thomsen H, Johnson NP, von Hippel PH, Aspuru-Guzik A, Marcus AH
Nucleic Acids Res 2013 Jan;41(2):995-1004
Fifty years of DNA "Breathing": Reflections on old and new approaches.
von Hippel PH, Johnson NP, Marcus AH
Biopolymers 2013 Dec;99(12):923-54
Single-molecule FRET and linear dichroism studies of DNA breathing and helicase binding at replication fork junctions.
Phelps C, Lee W, Jose D, von Hippel PH, Marcus AH
Proc Natl Acad Sci U S A 2013 Oct 22;110(43):17320-5
Assembly and subunit stoichiometry of the functional helicase-primase (primosome) complex of bacteriophage T4.
Jose D, Weitzel SE, Jing D, von Hippel PH
Proc Natl Acad Sci U S A 2012 Aug 21;109(34):13596-601
Development of a "modular" scheme to describe the kinetics of transcript elongation by RNA polymerase.
Greive SJ, Goodarzi JP, Weitzel SE, von Hippel PH
Biophys J 2011 Sep 7;101(5):1155-65
Fitting experimental transcription data with a comprehensive template-dependent modular kinetic model.
Greive SJ, Dyer BA, Weitzel SE, Goodarzi JP, Main LJ, von Hippel PH
Biophys J 2011 Sep 7;101(5):1166-74
DNA conformational changes at the primer-template junction regulate the fidelity of replication by DNA polymerase.
Datta K, Johnson NP, von Hippel PH
Proc Natl Acad Sci U S A 2010 Oct 19;107(42):17980-5
DNA models of trinucleotide frameshift deletions: the formation of loops and bulges at the primer-template junction.
Baase WA, Jose D, Ponedel BC, von Hippel PH, Johnson NP
Nucleic Acids Res 2009 Apr;37(5):1682-9
Spectroscopic studies of position-specific DNA "breathing" fluctuations at replication forks and primer-template junctions.
Jose D, Datta K, Johnson NP, von Hippel PH
Proc Natl Acad Sci U S A 2009 Mar 17;106(11):4231-6
The protein factors MBNL1 and U2AF65 bind alternative RNA structures to regulate splicing.
Warf MB, Diegel JV, von Hippel PH, Berglund JA
Proc Natl Acad Sci U S A 2009 Jun 9;106(23):9203-8
Monitoring RNA transcription in real time by using surface plasmon resonance.
Greive SJ, Weitzel SE, Goodarzi JP, Main LJ, Pasman Z, von Hippel PH
Proc Natl Acad Sci U S A 2008 Mar 4;105(9):3315-20
Transcriptional pausing caught in the act.
von Hippel PH
Cell 2006 Jun 16;125(6):1027-8
A quantitative description of the binding states and in vitro function of antitermination protein N of bacteriophage lambda.
Conant CR, Van Gilst MR, Weitzel SE, Rees WA, von Hippel PH
J Mol Biol 2005 May 20;348(5):1039-57