Name: how protein shape controls function
Uploaded: 2020-09-24T15:06:53.000Z
Duration: 2 min 15 s
Channel: JoVE

蛋白质是通过肽键连接在一起的 氨基酸聚合物。大多数蛋白质折叠成特定的三维结构 来执行它们的功能。蛋白质结构分为四类：一级、二级、三级和四级。蛋白质中氨基酸的线性序列 是它的一级结构。这些序列按照聚合物合成顺序读取，从氮端，也就是游离氨基端，到碳端，也就是游离羧基端。通过一个氨基酸羰基上的氧 和另一个氨基酸氨基上的氢 之间的氢键 形成了二级结构。常见的二级结构包括α-螺旋和β-折叠 片。这些结构和其他连接结构，例如β-转角，进一步相互作用形成蛋白质的三维结构，称为三级结构。三级结构的形成是 由于氨基酸的 R 基团之间的 相互作用。具有相反电荷的 R-基团可以形成离子键，两个半胱氨酸中的硫可以形成 共价二硫键。其他促进因素包括 疏水侧链之间的疏水相互作用和 极性侧链之间的氢键。另外，一些蛋白质形成四级结构，即两条或多条多肽链的集合体。例如，血红蛋白是由四个亚基组成的蛋白质，两个α和两个β。科学家可以利用蛋白质的结构 来预测它在细胞中的功能和位置。细胞质中的蛋白质表面有亲水氨基酸，与细胞质中的水相互作用，并具有疏水核心。相反，细胞膜中的蛋白质表面 通常有疏水氨基酸，与膜中的甘油磷脂相互作用，并具有亲水核心。

<ol>
	<li>纳尔逊，D. L.和考克斯，M. M. （2008）。Lehninger 生物化学原理（第 5 版）。WH 弗里曼。第 113-140 页</li>
	<li>在所有四个血红素处与氧结合的 T 状态血红蛋白的晶体结构.Paoli， M.， Liddington， R.， Tame， J.， Wilkinson， A.， Dodson， G. （1996） J Mol Biol 256:775</li>
</ol>

蛋白质和蛋白质结构

蛋白质是生活系统中最丰富的有机分子之一，具有所有巨分子最多样化的功能范围。 蛋白质可以是结构，调节，收缩或保护性的。 它们可以在运输，储存或膜中使用；也可以是毒素或酶。 他们的结构和他们的职能一样大不相同。 但是，它们都是以线性顺序排列的氨基酸聚合物。 
 蛋白质的形状对其功能至关重要。 例如，一种酶可以在其活性部位粘结特定基体。 如果由于局部蛋白质结构变化或总体蛋白质结构变化而改变此活性部位，则酶可能无法与基质结合。 为了了解蛋白质如何获得最终形状或构象，我们需要了解蛋白质结构的四个级别：一级、二级、三级和四级。 
 一级结构 
 氨基酸在多肽链中的独特序列是其主要结构。 例如，胰腺激素胰岛素有两个多肽链 A 和 B ，它们通过二硫化物键连接在一起。 A 链的 N 端子氨基酸是甘氨酸；而 C 端子氨基酸是芦笋。  A 和 B 链中的氨基酸序列是胰岛素特有的。 
 对蛋白质进行编码的基因最终决定了每种蛋白质的独特序列。 基因编码区的核苷酸序列发生变化可能导致向生长中的多肽链添加不同的氨基酸，从而导致蛋白质结构和功能发生变化。 在镰状细胞贫血中，血红蛋白 β 链具有单个氨基酸替代品，从而导致蛋白质结构和功能发生变化。 具体而言， β 链中的缬氨酸可替代氨基酸谷氨酸谷氨酸。 由于链中的一种氨基酸发生了这种变化，血红蛋白分子形成了扭曲双腔体或圆盘形红细胞的长纤维，并导致它们采用新月形或“镰刀”形，从而阻塞血管。 这可能会导致无数严重的健康问题，如对这种疾病患者的呼吸困难，头晕，头痛和腹痛。 
 二级结构 
 某些地区的多肽局部折叠导致蛋白质的二次结构。 最常见的是 α - 螺旋和 β - 褶皱的图纸结构。 这两个结构都由氢键固定。 氢键形成于一种氨基酸和另一种氨基酸 (沿着链更远的地方为四种氨基酸) 的碳基组中的氧原子之间。 
 每一个螺旋线的螺旋转弯都有 3.6 个氨基酸残留物。 多肽的 R 组 (变异组) 从 α - 螺旋链中伸出。 在 β 层板中，多肽链主干上原子之间的氢键形成了“褶皱”。 R 组附着在碳化合物上，并延伸到褶皱的上方和下方。 褶皱段相互平行或反平行，氨基组中的部分正氢原子和肽骨干碳基组中的部分负氧原子之间形成氢键。 α - 螺旋和 β - 褶皱的薄板结构存在于大多数球蛋白和纤维蛋白中，它们在结构上发挥着重要作用。 
 三级结构 
 多肽独特的三维结构是其第三层结构。 这种结构的部分原因是多肽链工作中的化学相互作用。 主要是， R 组之间的相互作用形成了蛋白质的化合物三维三维三维结构。 所涉及的氨基酸中的 R 组的性质可以抵消形成标准二级结构所描述的氢键。 例如，具有相似电荷的 R 组相互排斥，具有不同电荷的 R 组相互吸引 (ionic 键)。 当蛋白质折叠发生时，非极性氨基酸的疏水 R 组位于蛋白质的内饰中；而亲水 R 组位于外侧。 半胱氨酸侧链之间的相互作用在存在氧气的情况下形成二硫化联接，这是蛋白质折叠过程中形成的唯一共价键。 
 所有这些相互作用 (弱和强) 决定了蛋白质的最终三维形状。 当蛋白质失去三维形状时，它可能不再起作用。 
 四级结构 
 从本质上讲，一些蛋白质来自多种多肽或亚单位，这些亚单位的相互作用形成四元结构。 各分队之间的微弱互动有助于稳定整体结构。 例如，胰岛素 (球蛋白) 有氢和二硫键的组合，这会导致胰岛素大部分粘在球形中。 胰岛素以单个多肽形式开始，在形成将其余链固定在一起的二硫化物链结后，在出现平移后修饰时会丢失一些内部序列。 β ，丝绸 (一种纤维蛋白) 的层板结构是由不同链之间的氢键产生的。 
 本文改编自<a href="https://openstax.org/books/biology-2e/pages/3-4-proteins"> Openstax, 生物学 2e, 第 3.4 章：蛋白质</a>。

蛋白质是生物系统中最丰富的有机分子之一，其功能多样性在所有大分子中居于首位。蛋白质可能……

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Protein and Protein Structure

how protein shape controls function

Proteins are a major class of organic molecules in living systems, and their shape helps determine what they do. They can act as structural, regulatory, contractile, or protective molecules. They also take part in transport, storage, membranes, toxins, and enzymes. All proteins are polymers of amino acids arranged in a linear sequence.

A protein’s function depends on its three-dimensional form. For example, an enzyme works when its active site can bind a specific substrate. If local changes or larger changes in protein structure alter that site, the enzyme may no longer bind the substrate. To understand how a protein reaches its final conformation, it helps to study four levels of structure: primary, secondary, tertiary, and quaternary.

Primary structure is the unique amino acid sequence of a polypeptide chain. In insulin, the pancreatic hormone, there are two polypeptide chains, A and B, held together by disulfide bonds. The A chain begins with glycine at the N terminus and ends with asparagine at the C terminus. The gene that encodes a protein determines this sequence, so a change in the coding region can add a different amino acid and change protein structure and function. Sickle cell anemia shows this clearly. In the hemoglobin beta chain, valine replaces glutamic acid, and that single change leads hemoglobin to form long fibers that distort red blood cells into a sickle shape and clog blood vessels. This can cause breathlessness, dizziness, headaches, and abdominal pain.

Secondary structure comes from local folding in parts of the polypeptide chain. The most common forms are the alpha helix and the beta-pleated sheet. Hydrogen bonds hold both forms in place. These bonds form between the oxygen in a carbonyl group on one amino acid and another amino acid four positions farther along the chain. In an alpha helix, each turn contains 3.6 amino acid residues, and the R groups point outward. In a beta-pleated sheet, hydrogen bonds form along the backbone to create pleats. The R groups extend above and below the folds, and the strands can align parallel or antiparallel. These structures are common in globular and fibrous proteins, where they provide support.

Tertiary structure is the full three-dimensional shape of one polypeptide. Interactions among R groups are the main force behind this folding. Like charges repel, unlike charges attract through ionic bonds, and hydrophobic R groups tend to move into the protein interior while hydrophilic R groups stay outside. Cysteine side chains can also form disulfide linkages in the presence of oxygen, and this is the only covalent bond formed during protein folding. Together, these weak and strong interactions set the final shape. If a protein loses that shape, it may no longer work.

Some proteins also form quaternary structure. This happens when several polypeptide subunits join together. Weak interactions between the subunits help stabilize the overall protein. Insulin is one example of a globular protein with hydrogen and disulfide bonds that help it form a mostly ball-like shape. It begins as a single polypeptide and then loses some internal sequences during post-translational modification after the disulfide linkages form and hold the remaining chains together. Silk is another example, but it is a fibrous protein with a beta-pleated sheet structure created by hydrogen bonding between different chains.

How Protein Shape Controls Function

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protein and protein structure

Proteins are a major class of organic molecules in living systems, and their shape helps determine what they do. They can act as structural, regulatory, contractile, or protective molecules. They also take part in transport, storage, membranes, toxins, and enzymes. All proteins are polymers of amino acids arranged in a linear sequence. A protein’s function depends on its three-dimensional form. For example, an enzyme works when its active site can bind a specific substrate. If local changes or...

amino acids

Amino Acids and Protein Building

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polymers

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key terms and concepts

Explore how amino acid sequence, folding, and subunit interactions shape proteins. Learn the four levels of protein structure with insulin and sickle cell examples.

How Protein Shape Controls Function | JoVE K12

chemistry

JoVE Core 化学通过简单明了且通俗易懂的动画视频课程，将普通化学概念带入到现实生活当中。此外，在科学家行动视频中，我们演示了在实验室中进行的经典和原始研究实验。

How Protein Shape Controls Function

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