分子与细胞生物学 5 - L3d Proteins (2)

3 Proteins (2) - Tertiary & Quaternary structure, Protein Folding

本章的内容是蛋白质，本节将继续讨论蛋白质的高级结构以及蛋白质折叠。下一节将讨论蛋白质的调节与控制。如果有不太明白的或者有错误的地方随时来找UP主喔~

文集本部分的参考文献Essential Cell Biology, 5th ed. Alberts, et al. 2019. 部分内容来自khanacademy与维基百科.

封面图：https://sites.google.com/site/fabiopietrucci/Home/research/proteinfolding

3d Tertiary & Quaternary structure, Protein Folding 

Three principles of protein folding

    Hydrophobic - towards the inside (Hydrophobic effect, non-polar gets to non-polar parts while polar gets to polar parts.)

    Non-covalent bonds pin secondary, tertiary, quaternary structures in place

    In quaternary structure, subunits have complementary shapes and charges

The hydrophobic effect 疏水作用，在生物中非常非常重要！

    Folded conformation in aqueous environment:

            Hydrophobic core (non-polar side chains) - away from the water

            + surface (polar / charged side chains)

    Compacts the polypeptide chain, forming a hydrophobic core

Non-covalent bonds pin secondary, tertiary, quaternary structures in place

        Primary: covalent, peptide bonds

        Secondary:

            H-bonds between backbone polar groups (O in carboxyl and H in amino)

        Tertiary/Quaternary:

            All types of non-covalent bonds between side chains, backbone groups

                    Ionic bonds, dispersion force, H-bonds

            Also disulfide bonds which is covalent

                    Outside of the cell

                    Bind itself in the tertiary, and between proteins in the quaternary

Secondary structures pack together to form tertiary structure

        Interact via side chains between them

        Amino acid sequence determines protein fold

The overall 3-D structure of a polypeptide is called its tertiary structure.

Complementary shapes and charges

        Specific to quaternary structures - proteins in a Protein Complex

        Shape: fit “puzzle” pieces

                Tight packing, subunits fit together snugly, no open spaces

                Maximized dispersion forces - help hold two protein together (fit puzzle)

Charges: ionic bonds

Denaturation

    Unfolding - Usually needs heat

    Loss of secondary and tertiary structures

    Becomes an extended polypeptide chain

    No correct 3-D conformation, no function

3-D structure is critical for protein function - eg substrate specific binding pockets

Cofactors

    Non-protein components, needed for protein functions

    Have chemical properties, not available with side chains alone

    Eg heme group with iron binds oxygen

Domains: A sub-part of a polypeptide

- Each domain

    Folds independently - has its own hydrophobic core

    Carries out a different sub-function

One polypeptide - 1 covalently connected peptide backbone - can be a two-domain protein (two hydrophobic cores)

Two polypeptide - no covalent connection - can be a two-subunit protein complex (two hydrophobic cores)

    No covalent connection between red & blue subunits. There are two domains in each subunit: top - binding DNA; bottom - binding lactose

    Be careful: 2 subunits 1 domain each looks similar as 1 subunit 2 domains each

Unfolded proteins (exposed to water) tend to aggregate

    Exposed hydrophobic regions stick together

    Multiple proteins end up in a tangled mass

Chaperone - proteins that help other proteins to fold.

    Protect hydrophobic surfaces from water before the protein is properly folded

    Prevent unwanted hydrophobic interactions - Do not determine specific structure