Về vai trò của một methionine bảo tồn trong cơ chế kết hợp Na+ của một đồng phân transport dẫn truyền thần kinh
Tóm tắt
Các vận chuyển axit amin kích thích (EAAT) đóng một vai trò chính trong giao tiếp synap glutamatergic. Được thúc đẩy bởi các gradient cation xuyên màng, các vận chuyển này xúc tác việc tái hấp thu glutamate từ khe synap khi neurotransmitter này đã được sử dụng cho việc tín hiệu. Hai thập kỷ trước, những nghiên cứu tiên phong trong phòng thí nghiệm Kanner đã xác định một methionine bảo tồn trong miền xuyên màng là yếu tố chủ chốt ảnh hưởng đến tỷ lệ và đặc hiệu của vòng tuần hoàn substrate; sau đó, các công trình cấu trúc, đặc biệt là những đồng phân prokaryotic GltPh và GltTk, đã chỉ ra rằng methionine này có liên quan đến việc phối hợp với một trong ba ion Na+ được đồng vận chuyển cùng với substrate. Dù điều này là cực kỳ bất thường, sự tồn tại của tương tác này nhất quán với các phân tích sinh lý học của GltPh cho thấy rằng các đột biến của methionine này giảm đi tính hợp tác trong việc liên kết giữa các substrate và Na+. Tuy nhiên, vẫn chưa rõ liệu methionine thú vị này có ảnh hưởng đến nhiệt động lực học của phản ứng vận chuyển, tức là, tỷ lệ stoichiometry substrate:ion của nó, hay nó chỉ đơn thuần thúc đẩy một động lực học cụ thể trong phản ứng liên kết, mà trong khi có ảnh hưởng đến tỷ lệ vòng tuần hoàn, không giải thích một cách cơ bản cơ chế kết hợp ion của lớp vận chuyển này. Tại đây, các nghiên cứu về GltTk sử dụng các phương pháp thực nghiệm và tính toán đều đi đến kết luận rằng giả thuyết sau là khả dĩ nhất, và đặt nền tảng cho các nỗ lực trong tương lai để khám phá cơ chế bên dưới.
Từ khóa
#EAAT #glutamate #neurotransmitter #Na+ coupling #GltPh #GltTk #thermodynamicsTài liệu tham khảo
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