Protein Tertiary and Quaternary Structures: -Analysis of Many Globular Proteins Reveals Common Structural Patterns

For the beginning student, the very complex tertiary structures of globular proteins much larger than those shown in Figure 4–18 are best approached by focusing on structural patterns that recur in different and often unrelated proteins. The three-dimensional structure of a typical globular protein can be considered an assemblage of polypeptide segments in the α-helix and β-sheet conformations, linked by connecting segments. The structure can then be described to a first approximation by defining how these segments stack on one another and how the segments that connect them are arranged. This formalism has led to the development of databases that allow informative comparisons of protein structures, complementing other databases that permit comparisons of protein sequences. An understanding of a complete three-dimensional structure is built upon an analysis of its parts. We begin by defining terms used to describe protein substructures, then turn to the folding rules elucidated from analysis of the structures of many proteins. Supersecondary structures, also called motifs or simply folds, are particularly stable arrangements of several elements of secondary structure and the connections between them. There is no universal agreementamong biochemists on the application of the three terms, and they are often used interchangeably. The terms are also applied to a wide range of structures. Recognized motifs range from simple to complex, sometimes appearing in repeating units or combinations. A single large motif may comprise the entire protein. We have already encountered one well-studied motif, the coiled coil of -keratin, also found in a number of other proteins. Polypeptides with more than a few hundred amino acid residues often fold into two or more stable, globular units called domains. In many cases, a domain from a large protein will retain its correct three-dimensional structure even when it is separated (for example, by proteolytic cleavage) from the remainder of the polypeptide chain. A protein with multiple domains may appear to have a distinct globular lobe for each domain (Fig. 4–19), but, more commonly, extensive contacts between domains make individual domains hard to discern. Different domains often have distinct functions, such as the binding of small molecules or interaction with other proteins. Small proteins usually have only one domain (the domain is the protein). Folding of polypeptides is subject to an array of physical and chemical constraints. A sampling of the prominent folding rules that have emerged provides an opportunity to introduce some simple motifs.

1. Hydrophobic interactions make a large contribution to the stability of protein structures. Burial of hydrophobic amino acid R groups so as to exclude water requires at least two layers of secondary structure. Two simple motifs, the -- loop and the -corner (Fig. 4–20a), create two layers. 2. Where they occur together in proteins, helices α and β sheets generally are found in different structural layers. This is because the backbone of a polypeptide segment in the β conformation (Fig. 4–7) cannot readily hydrogen-bond to an helix aligned with it.

FIGURE 4–19 Structural domains in the polypeptide troponin C. (PDB ID 4TNC) This calcium-binding protein associated with muscle has separate calcium-binding domains, indicated in blue and purple.

FIGURE 4–20 Stable folding patterns in proteins. (a) Two simple and common motifs that provide two layers of secondary structure. Amino acid side chains at the interface between elements of secondary structure are shielded from water. Note that the strands in the β-α-β loop tend to twist in a right-handed fashion. (b) Connections between β strands in layered β sheets. The strands are shown from one end, with no twisting included in the schematic. Thick lines represent connections at the ends nearest the viewer; thin lines are connections at the far ends of the β strands. The connections on a given end (e.g., near the viewer) do not cross each other. (c) Because of the twist in β strands, connections between strands are generally right-handed. Lefthanded connections must traverse sharper angles and are harder to form. (d) Two arrangements of β strands stabilized by the tendency of the strands to twist. This β barrel is a single domain of -hemolysin (a pore-forming toxin that kills a cell by creating a hole in its mem brane) from the bacterium Staphylococcus aureus (derived from PDB ID 7AHL). The twisted β sheet is from a domain of photolyase (a protein that repairs certain types of DNA damage) from E. coli (derived from PDB ID 1DNP).

3. Polypeptide segments adjacent to each other in the primary sequence are usually stacked adjacent to each other in the folded structure. Although distant segments of a polypeptide may come together in the tertiary structure, this is not the norm.

4. Connections between elements of secondary structure cannot cross or form knots (Fig. 4–20b).

5. The β conformation is most stable when the individual segments are twisted slightly in a right-handed sense. This influences both the arrange ment of β sheets relative to one another and the path of the polypeptide connection between them. Two parallel β strands, for example, must be connected by a crossover strand (Fig. 4–20c). In principle, this crossover could have a right- or left-handed conformation, but in proteins it is almost always right-handed. Right-handed connections tend to be shorter than left-handed connections and tend to bend through smaller angles, making them easier to form. The twisting of β sheets also leads to a characteristic twisting of the structure formed when many segments are put together. Two examples of resulting structures are the β barrel and twisted β sheet (Fig. 4–20d), which form the core of many larger structures.

Following these rules, complex motifs can be built up from simple ones. For example, a series of β - α - β loops, arranged so that the β  strands form a barrel, creates a particularly stable and common motif called the α / β barrel (Fig. 4–21). In this structure, each parallel seg ment is attached to its neighbor by an -helical segment. All connections are right-handed. The α / β barrel is found in many enzymes, often with a binding site for a cofactor or substrate in the form of a pocket near one end of the barrel. Note that domains exhibiting similar folding patterns are said to have the same motif even though their constituent helices and sheets may differ in length.

FIGURE 4–21 Constructing large motifs from smaller ones. The α / β barrel is a common motif constructed from repetitions of the simpler β - α - β loop motif. This α / β barrel is a domain of the pyruvate kinase (a glycolytic enzyme) from rabbit (derived from PDB ID 1PKN). β-α -β loop motif. This α / β barrel is a domain of the pyruvate kina

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اخبار العتبة العباسية المقدسة

مؤسّسة الوافي تُهدي مكتبةَ مسجد الكوفة نسخةً من موسوعة فتوى الدفاع الكفائي

المجمع العلمي يقيم برنامج (سراج المنتظرين) في محافظة المثنى

قسم الشؤون الفكرية ينظم ندوة فكرية عن أبعاد نهضة الإمام الصادق (عليه السلام)

العتبة العباسية المقدسة تناقش تكثيف جهودها الإغاثية لدعم الشعبين الإيراني واللبناني

المزيد

الآخبار الصحية

دواء جديد يحمي القلب ويعزز علاج السرطان في آن واحد

سر غذائي بسيط لحماية القلب مع التقدم في العمر

علامات تشير إلى اختلال عمل الغدة الدرقية

السمنة واللقاحات.. دراسة تكشف تأثيراً سلبياً

المزيد

الآخبار التكنلوجية

البعوض في آيسلندا إشارة مبكرة على تحولات بيئية في القطب الشمالي

صاروخ يطلق قمرا اصطناعيا في مدار خاطئ

"أوبن إيه آي" تطلق نموذجا للعلوم الحيوية واكتشاف الأدوية

تفوق على البشر.. روبوت يحطم الرقم القياسي لسباق نصف ماراثون !

المزيد

مواضيع ذات صلة

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Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins: -Oxygen Binding to Hemoglobin Is Regulated by 2,3-Bisphosphoglycerate

Protein Denaturation and Folding: - Loss of Protein Structure Results in Loss of Function

Protein Tertiary and Quaternary Structures: -There Are Limits to the Size of Proteins

Protein Tertiary and Quaternary Structures: -Protein Quaternary Structures Range from Simple Dimers to Large Complexes

Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins: -Protein-Ligand Interactions Can Be Described Quantitatively

Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins:- Myoglobin Has a Single Binding Site for Oxygen

Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins:- Oxygen Can Be Bound to a Heme Prosthetic Group

Protein Denaturation and Folding:- Some Proteins Undergo Assisted Folding

Protein Denaturation and Folding:- Polypeptides Fold Rapidly by a Stepwise Process

Protein Denaturation and Folding: - Amino Acid Sequence Determines Tertiary Structure