• Home   /  
  • Archive by category "1"

Denatured Protein Research Paper

Alfred E. Mirsky, 1960s

In 1935, as a result of being prompted toward the biological sciences in order to keep his Rockefeller Foundation funding, Linus Pauling began his research on proteins. Hemoglobin, the oxygen-binding agent in blood, was his first target; but as he became more aware of the complex nature and diversity of proteins, he began contemplating broader topics related to the subject – one of which was the theory of protein denaturation.

In the spring of 1935, Pauling traveled to the Rockefeller Institute in New York City, where he met Dr. Alfred Mirsky. Mirsky was a Rockefeller scientist who had previously conducted denaturation research, and because of his new interest in the subject, Pauling arranged for Mirsky to spend fifteen months working with him at Caltech. Although initially hesitant, Mirsky eventually agreed, and the pair began collaborating in the summer of 1935.

In July 1936, the duo’s paper, titled “On the Structure of Native, Denatured, and Coagulated Proteins” was published in the Proceedings of the National Academy of Sciences.  In this paper, the authors loosely describe protein denaturation as “the loss of certain highly specific properties by the native protein,” and provide examples of the types of changes that have been experimentally observed.

In so doing, Pauling and Mirsky point out that while many proteins in their native form have been crystallized, no denatured protein exist in this state. Likewise, in proteins that act as enzymes, denaturation causes a disappearance of the enzymatic activity.  And one fact that was of particular interest to Pauling was that the process of denaturation is occasionally reversible.

Early Pauling notes on the characteristics of protein denaturation, ca. 1935

As researchers are now aware, any given protein has a certain structure – or rather, four different structural levels – that needs to be maintained in order for the molecule to function correctly. Although this crucial bit of information was still unknown at the time of Pauling and Mirsky’s research, the authors essentially touch on this exact detail in their 1936 paper:

Our conception of a native protein molecule (showing specific properties) is the following. The molecule consists of one polypeptide chain [the amino acid sequence] which continues without interruption throughout the molecule (or in certain cases, of two or more such chains); this chain is folded into a uniquely defined configuration, in which it is held by hydrogen bonds…

The collaborators further posited that, as a result of this “structure equals function” characteristic of proteins, denaturation is “characterized by the absence of a uniquely defined configuration” and can be accomplished in a number of different ways, including heating, subjection to ultraviolet light, or an attack by certain reagents.

In presenting their theory of denaturation, Pauling and Mirsky associated both the heating of the protein and its treatment with certain reagents, as leading to the disruption or complete rupturing of hydrogen bonds.  From there they pointed out that ultraviolet light is not able to break a sufficient quantity of hydrogen bonds, and therefore must affect the molecule differently – an impact which they predicted to be an attack on the main polypeptide chain. Consequently, they suggested that denaturation caused by ultraviolet light was irreversible, while methods that disrupt the more easily re-formed hydrogen bonds would be reversible.

Although Pauling and Mirsky weren’t correct in every aspect of their denaturation theory (ultraviolet light does not disturb the polypeptide chain, and denaturation involves more than just the disruption of hydrogen bonds), it provided a strong start for further work.  The Pauling-Mirsky theory also touched on many details of the structure of proteins in their native forms, a field of inquiry that would not be completely elucidated for many years to come.

For more information on Linus Pauling, please visit the Linus Pauling Online portal. For more information on Alfred Mirsky, visit his key participants page within the It’s in the Blood! A Documentary History of Linus Pauling, Hemoglobin, and Sickle Cell Anemia site.

Like this:

LikeLoading...

Related

Filed under: Hemoglobin & Sickle Cell Anemia, Structure of Proteins | Tagged: Alfred Mirsky, Linus Pauling, protein denaturation |

Citation data is made available by participants in Crossref's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search inSciFinder.

  • Overview of the Stability of α-Chymotrypsin in Different Solvent Media

    AwanishKumarPannuruVenkatesu

    Chemical Reviews2012112 (7), 4283-4307

    Abstract | Full Text HTML | PDF | PDF w/ Links

  • Molecular Mechanism for the Denaturation of Proteins by Urea

    JorgeAlmarzaLuisRinconAliBahsasFranciscoBrito

    Biochemistry200948 (32), 7608-7613

    Abstract | Full Text HTML | PDF | PDF w/ Links

  • Molecular Mechanism for the Denaturation of Proteins by Urea

    JorgeAlmarzaLuisRinconAliBahsasFranciscoBrito

    Biochemistry0 (proofing),

    Abstract | Full Text HTML

  • Plasticity of Amyloid Fibrils

    RonaldWetzel,ShankarammaShivaprasad, andAngela D.Williams

    Biochemistry200746 (1), 1-10

    Abstract | Full Text HTML | PDF | PDF w/ Links

  • Dominant forces in protein folding

    Ken A.Dill

    Biochemistry199029 (31), 7133-7155

    Abstract | PDF | PDF w/ Links

  • Bovine β-lactoglobulins in urea solution. Denaturation at pH 5.2 and 3.5

    H. A.McKenzieG. B.Ralston

    Biochemistry197312 (6), 1025-1034

    Abstract | PDF | PDF w/ Links

  • Conformational changes in proteins as measured by difference sedimentation studies. I. Technique for measuring small changes in sedimentation coefficient

    Marc W.KirschnerH. K.Schachman

    Biochemistry197110 (10), 1900-1919

    Abstract | PDF | PDF w/ Links

  • Thermodynamics of protein denaturation. Calorimetric study of the reversible denaturation of chymotrypsinogen and conclusions regarding the accuracy of the two-state approximation

    William MichaelJacksonJohn F.Brandts

    Biochemistry19709 (11), 2294-2301

    Abstract | PDF | PDF w/ Links

  • Thermal denaturation of myoglobin. I. Kinetic resolution of reaction mechanism

    Elias S.AwadDavid A.Deranleau

    Biochemistry19687 (5), 1791-1795

    Abstract | PDF

  • N-Acetylimidazole: A Reagent for Determination of “Free” Tyrosyl Residues of Proteins*

    James F.RiordanWarren E. C.WackerBert L.Vallee

    Biochemistry19654 (9), 1758-1765

    Abstract | PDF | PDF w/ Links

  • Magnetic Resonance Studies of the Interaction of the Manganous Ion with Bovine Serum Albumin*

    Albert S.MildvanMildredCohn

    Biochemistry19632 (5), 910-919

    Abstract | PDF | PDF w/ Links

  • The Relationship of Structure to the Effectiveness of Denaturing Agents for Proteins

    Julius A.GordonWilliam P.Jencks

    Biochemistry19632 (1), 47-57

    Abstract | PDF | PDF w/ Links

  • The Dissociation and Reconstitution of Aldolase*

    E.StellwagenH. K.Schachman

    Biochemistry19621 (6), 1056-1069

    Abstract | PDF | PDF w/ Links

  • The Kinetics of Protein Denaturation. I. The Behavior of the Optical Rotation of Ovalbumin in Urea Solutions1

    Richard B.SimpsonW.Kauzmann

    Journal of the American Chemical Society195375 (21), 5139-5152

    Abstract | PDF | PDF w/ Links

  • The Kinetics of Protein Denaturation. II. The Optical Rotation of Ovalbumin in Solutions of Guanidinium Salts

    J.SchellmanR. B.SimpsonW.Kauzmann

    Journal of the American Chemical Society195375 (21), 5152-5154

    Abstract | PDF | PDF w/ Links

  • Reactions between Mercuric Mercury and Cysteine and Glutathione. Apparent Dissociation Constants, Heats and Entropies of Formation of Various Forms of Mercuric Mercapto-Cysteine and -Glutathione

    W.StricksI. M.Kolthoff

    Journal of the American Chemical Society195375 (22), 5673-5681

    Abstract | PDF | PDF w/ Links

  • Elevation of the Intrinsic Viscosity of Peanut Protein by Treatment with Terephthalyl Dichloride2

    Godfrey E.Mann

    Journal of the American Chemical Society195375 (14), 3526-3529

    Abstract | PDF | PDF w/ Links

  • Studies of the Nucleation and Growth Reactions of Selected Types of Insulin Fibrils

    David F.WaughDarthea F.WilhelmsonSpencer L.CommerfordMuriel L.Sackler

    Journal of the American Chemical Society195375 (11), 2592-2600

    Abstract | PDF | PDF w/ Links

  • One thought on “Denatured Protein Research Paper

    Leave a comment

    L'indirizzo email non verrà pubblicato. I campi obbligatori sono contrassegnati *