Proteins - Many Structures, 1. A polypeptide is a polymer of amino acids connected to a specific sequence A protein's function depends on its specific conformation

roteins have many structures, classified into four levels: primary (the amino acid sequence), secondary (local structures like alpha-helices and beta-sheets), tertiary (the overall 3D shape of a single polypeptide chain), and quaternary (the arrangement of multiple polypeptide subunits)

1. Proteins - Many Structures, Many Functions A polypeptide is a polymer of amino acids connected to a specific sequence A protein's function depends on its specific conformation

2. Protein Objectives 7. 6. Distinguish proteins from the other classes of macromolecules and list the biological functions which members of this class perform List and be able to recognize the four major components of a typical amino acid and explain how amino acids may be grouped according to the nature of their side chain 9. 8. Identify a peptide bond and describe how it is formed Explain what determines protein conformation and why it is important Name the four levels of protein structure and briefly describe from what aspect of protein structure each is derived 10. Define denaturation and explain how proteins may be denatured

3. Introduction Proteins are instrumental in about everything that an organism does. structural support, storage transport of other substances intercellular signaling movement defense against foreign substances Proteins are the main enzymes in a cell and regulate metabolism by selectively accelerating chemical reactions. Humans have tens of thousands of different proteins, each with their own structure and function.

4. Proteins are the most structurally complex molecules known. — Each type of protein has a complex three- dimensional shape or conformation. All protein polymers are constructed from the same set of 20 monomers, called amino acids. Polymers of proteins are called polypeptides. A protein consists of one or more polypeptides folded and coiled into a specific conformation

5. 1. A polypeptide is a polymer of amino acids connected in a specific sequence Amino acids consist of four components attached to a central carbon, the alpha carbon. These components include a hydrogen atom, a carboxyl group, an amino group, and a variable R group (or side chain). — Differences i n R groups produce the 20 different amino acids. OH CH 2 OH H NH OH CH 3

6. The twenty different R groups may be as simple as a hydrogen atom (as in the amino acid glutamine) to a carbon skeleton with various functional groups attached. The physical and chemical characteristics of the R group determine the unique characteristics of a particular amino acid.

7. One group of amino acids has hydrophobic R groups. Glycirs(Gly) Alanine(Ala) Yaline(Yal) Leucine(Leu) IzoIevcire(IIe) IJethionine(¥rt) Phenylalani e(Phe) T‹yplephan{T›p) P‹oli‹e(P‹e)

8. Another group of amino acids has polar R groups, making them hydrophilic.

9. •The last group of amino acids includes those with functional groups that are charged (ionized) at cellular pH. Some R groups are bases, others are acids.

10. •Amino acids are joined together when a dehydration reaction removes a hydroxyl group from the carboxyl end of one amino acid and a hydrogen from the amino group of another. The resulting covalent bond is called a peptide bond. OH OU Am no end (N- terminus) (b) Carboxy end (C•terminus) chains

11. Repeating the process over and over creates a long polypeptide chain. — At one end is an amino acid with a free amino group the (the N- terminus) and at the other is an amino acid with a free carboxyl group the (the C- terminus). The repeated sequence (N- C- C) is the polypeptide backbone. Attached to the backbone are the various R groups. Polypeptides range in size from a few monomers to thousands.

12. A protein's function depends on its specific conformation A functional proteins consists of one or more polypeptides that have been precisely twisted, folded, and coiled into a unique shape. It is the order of amino acids that determines what the three- dimensional conformation will be. تتكون البروتينات الوظيفية من واحد أو أكثر من عديد الببتيدات التي تم لفها بدقة وطيها ولفائها في شكل فريد.
إن ترتيب الأحماض الأمينية هو الذي يحدد ما سيكون عليه التشكل ثلاثي الأبعاد.

13. A protein's specific conformation determines its function . التشكل المحدد للبروتين يحدد وظيفتها. In almost every case, the function depends on its ability to recognize and bind to some other molecule. في كل حالة تقريبا ، تعتمد الوظيفة على قدرتها على التعرف على جزيء آخر وربطه For example, antibodies bind to particular foreign substances that fit their binding sites. Enzyme recognize and bind to specific substrates, facilitating a chemical reaction. Neurotransmitters pass signals from one cell to another by binding to receptor sites on proteins in the membrane of the receiving cell . على سبيل المثال ، ترتبط الأجسام المضادة بمواد غريبة معينة تناسب مواقع الارتباط الخاصة بها.
يتعرف الإنزيم على ركائز معينة ويرتبط بها ، مما يسهل التفاعل الكيميائي.
تمرر الناقلات العصبية الإشارات من خلية إلى أخرى عن طريق الارتباط بمواقع المستقبلات على البروتينات الموجودة في غشاء الخلية المستقبلة.

14. Leveis Protein Structure Primary structure Secondary structure Tertiary structure are used to organize the folding within a single polypeptide. Quarternary structure arises when two or more polypeptides join to form a protein. ينشأ الهيكل الرباعي عندما ينضم اثنان أو أكثر من عديد الببتيدات لتشكيل بروتين.

15. The primary structure of a protein is its u n . ique . mi •'- ' •'» *H N - “ ” Amino end ,.- .’- ..ta_ sequence of amino acids. Lysozyme, an enzyme that attacks bacteria, consists on a polypeptide chain of 129 amino acids. The precise primary structure of a protein is determined by inherited genetic information. '• .- •- ,_, ” - „ Carboxyl end

16. Even a slight change in primary structure can aXect a protein's conformation and ability to function. حتى التغيير الطفيف في التركيب الأساسي يمكن أن يؤثر على تشكل البروتين وقدرته على العمل. In individuals with sickle cell disease, abnormal hemoglobins, oxygen- carrying proteins, develop because of a single amino acid substitution. في الأفراد المصابين بمرض فقر الدم المنجلي ، يتطور الهيموجلوبين غير الطبيعي ، والبروتينات الحاملة للأكسجين ، بسبب استبدال واحد بالحمض الأميني — These abnormal hemoglobins crystallize, deforming the red blood cells and leading to clogs in tiny blood vessels. تتبلور هذه الهيموجلوبين غير الطبيعي ، مما يؤدي إلى تشويه خلايا الدم الحمراء ويؤدي إلى انسداد في الأوعية الدموية الدقيقة.

17. Val t His \ Leu Thr Pro Glu t Glu val § His é Leu 1 Thr j Pro I’. .’" $l Glu loom \Oym ' • ' ' ' ' 1 2 3 4 5 6 7 (a) Normal red blood cells and the primary structure of normal hemoglobin 1 2 3 4 5 7 (b) Sickled red blood cells and the primary structure of sickle- cell hemoglobin

18. The secondary structure of a protein results from hydrogen bonds at regular intervals along the polypeptide backbone. ينتج الهيكل الثانوي للبروتين عن روابط هيدروجينية على فترات منتظمة على طول العمود الفقري للعديد الببتيد. Typical shapes that develop from secondary structure are coils (an alpha helix) or folds (beta pleated sheets). الأشكال النموذجية التي تتطور من
الهيكل الثانوي عبارة عن ملفات (حلزون ألفا) أو طيات
(بيتا مطوي
الأوراق).

19. The structural properties of silk are due to beta pleated sheets. الخصائص الهيكلية للحرير ترجع إلى بيتا
صفائح مطوي. — The presence of so many hydrogen bonds makes each silk fiber stronger than steel. إن وجود العديد من الروابط الهيدروجينية يجعل كل ألياف حرير أقوى من الفولاذ.

20. Tertiary structure is determined by a variety of interactions among R groups and between R groups and the polj/oeatide backbone. — These interactions include hydrogen bonds among polar and/or charged areas, ionic bonds between charged R groups, and hydrophobic interactions and van der Waals interactions amon hydrophobic R groups. bond — CH 2 — as— CH 2 — O — CH 2 —CH 2 — CH 2 — CH 2 Nit C C— CH 2 — O

21. While these three interactions are relatively weak, disulfide bridges, strong covalent bonds that form between the sulfhydryl groups (SH) of cysteine monomers, stabilize the structure. C H I * c- on CH 2 I phobic HIC CHP P lypepticie backbone

22. Quarternary structure results from the aggregation of two or more polypeptide subunits. Collagen is a fibrous protein of three polypeptides that are supercoiled like a rope. This provides the structural strength for their role in connective tissue. Hemoglobin is a globular protein with two copies of two kinds of polypeptides. (a) Oll8§gfi

23. (b) Sœondary abucture țc) Tørtiæy øłrtmturø - -

24. A protein's conformation can change in response to the physical and chemical conditions. يمكن أن يتغير شكل البروتين استجابة للظروف الفيزيائية والكيميائية. Changes in pH, salt concentration, temperature, or other factors can unravel or denature a protein. يمكن أن تؤدي التغيرات في درجة الحموضة أو تركيز الملح أو درجة الحرارة أو عوامل أخرى إلى تفكيك البروتين أو تشويهه. These forces disrupt the hydrogen bonds, ionic bonds, and disulfide bridges that maintain the protein's shape. تعمل هذه القوى على تعطيل الروابط الهيدروجينية والروابط الأيونية وجسور ثاني كبريتيد التي تحافظ على شكل البروتين. Some proteins can return to their functional shape after denaturation, but others cannot, especially in the crowded environment of the cell. يمكن لبعض البروتينات العودة إلى شكلها الوظيفي بعد التمسخ ، لكن البعض الآخر لا يمكنه ذلك ، خاصة في البيئة المزدحمة للخلية. Usually denaturation is permanent عادة ما يكون التمسخ دائما

25. Denaturation Renaturation Denatured protein

26. In spite of the knowledge of the three- dimensional shapes of over 10,000 proteins, it is still difficult to predict the conformation of a protein from its primary structure alone. على الرغم من معرفة الأشكال ثلاثية الأبعاد لأكثر من 10,000 بروتين ، لا يزال من الصعب التنبؤ بتشكل البروتين من هيكله الأساسي وحده. — Most proteins appear to undergo several intermediate stages before reaching their “mature" configuration. يبدو أن معظم البروتينات تمر بعدة مراحل وسيطة قبل أن تصل إلى تكوينها "الناضج".

27. The folding of many proteins is protected by chaperonin proteins that shield out bad influences. طي العديد من البروتينات محمي بواسطة بروتينات الشابرونين التي تحمي التأثيرات السيئة. Chaperonin @ An unfolded The cap attaches to that The cap comes (fully assembled) polypeptide end, causing the cylinder ofl, and the enters the to change shape in such properly folded cylinder from a may that it creates a protein is ona end. hydrophilie environment raleacad. for the folding of the polypeptide.

28. A new generation of supercomputers is being developed to generate the conformation of any protein from its amino acid sequence or even its gene sequence. يتم تطوير جيل جديد من أجهزة الكمبيوتر العملاقة لتوليد تشكل أي بروتين من تسلسل الأحماض الأمينية أو حتى تسلسله الجيني. Part of the goal is to develop general principles that govern protein folding. جزء من الهدف هو تطوير مبادئ عامة تحكم طي البروتين. At present, scientists use X- ray crystallography to determine protein conformation. This technique requires the formation of a crystal of the protein being studied. The pattern of diñraction of an X- ray by the atoms of the crystal can be used to determine the location of the atoms and to build a computer model of its structure.

29. Diffractad X- rays y X- ray beam €fzystal Photographic film @ X- ray crystallography @ Electron density map @ X- ray diffraction pattern from the crystal of a protein @ A computer graphic modei oT the protein ribonuciease (purple) bound to a ehort strand of nucleic acid (green)

30. Test Your Skills. How well can you: Distinguish proteins from the other classes of macromolecules and list the biological functions which members of this class perform List and be able to recognize the four major components of a typical amino acid and explain how amino acids may be grouped according to the nature of their side chain Identify a peptide bond and describe how it is formed Explain what determines protein conformation and why it is important Name the four levels of protein structure and briefly describe from what aspect of protein structure each is derived Define denaturation and explain how proteins may be denatured