ヒトの卵泡刺激ホルモンの構造は,その受容体との複合体である
Qing R Fan1, Wayne A Hendrickson
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
Nature
|January 22, 2005
まとめ
この研究は,ヒトの卵泡刺激ホルモン (FSH) がその受容体に結合する構造を明らかにし,手と握手の相互作用を示しています. この構造的な洞察は,生殖シグナル伝達とホルモン受容体の特異性を理解する上で重要なものです.
科学分野:
- 構造生物学 構造生物学とは
- 生殖内分泌学 生殖内分泌学
- バイオケミストリー バイオケミストリー
背景:
- 卵泡刺激ホルモン (FSH) は哺乳類の繁殖に不可欠であり,Gタンパク質結合受容体を通して作用する.
- FSHとその受容体 (FSHR) の間の分子相互作用を理解することは,生殖生物学にとって不可欠です.
研究 の 目的:
- 人間のFSH-FSHR(HB) 複合体の高解像度構造を決定する.
- グリコプロテインホルモン受容体相互作用の結合モードと特異性決定因子の解明.
主な方法:
- 2.9-Aの解像度のX線結晶学.
- FSHR (FSHR(HB)) の細胞外ホルモン結合ドメインに結合した部分的にデグリコシル化されたヒトFSHの構造分析.
主要な成果:
- 構造は,FSHと長引く,曲がったFSHRとHBの間のハンドクラップ結合モードを明らかにします.
- 高い電荷密度を持つ大きな埋もれたインターフェース (2,600 A2) が観察されました.
- FSHは結合時に形状の変化を経験し,受容体活性化に関わるループに影響を与えます.
- 複合体は,結晶と溶液の中でダイマーを形成し,信号伝導に潜在的に関与します.
結論:
- 観察された結合モードは,すべてのグリコプロテインホルモンに保存されるように提案されています.
- 特殊性は,FSHのアルファおよびベータサブユニットの両方を含む主要な相互作用によって媒介されます.
- 構造的洞察は,FSHシグナル伝達と潜在的な治療目標を理解するための基礎を提供します.
関連する概念動画
Antibody Structure
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Fertilization
During fertilization, an egg and sperm cell fuse to create a new diploid structure. In humans, the process occurs once the egg has been released from the ovary, and travels into the fallopian tubes. The process requires several key steps: 1) sperm present in the genital tract must locate the egg; 2) once there, sperm need to release enzymes to help them burrow through the protective zona pellucida of the egg; and 3) the membranes of a single sperm cell and egg must fuse, with the sperm...
Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...
Antibody Structure
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Compounds Essential to Human Function
The human body is composed of cells that are fundamentally made up of several different molecules. These molecules are essential to carry out all physiological processes in the body and are broadly classified into organic and inorganic based on their chemical structures.
Inorganic Compounds Essential to Human Functioning
Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic, i.e., they do not have a carbon-hydrogen bond. Water...
Inorganic Compounds Essential to Human Functioning
Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic, i.e., they do not have a carbon-hydrogen bond. Water...
Nucleic Acid Structure
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...
DNA Structure
DNA has a double-helix structure. The...


