Shuguang Zhang | |
---|---|
Born | |
Known for | self-assembling peptides |
Academic background | |
Education | University of California, Santa Barbara (Ph.D.), Sichuan University (B.S.) |
Doctoral advisor | Eduardo Orias |
Academic work | |
Discipline | Biochemistry |
Sub-discipline | Molecular Architecture |
Institutions | Massachusetts Institute of Technology |
Website | https://www.media.mit.edu/people/shuguang/overview/ |
Shuguang Zhang is an American biochemist. He is at the MIT Media Lab's Laboratory for Molecular Architecture. [1] Shuguang Zhang's research focuses on designs of biological molecules,particularly proteins and peptides. He has published over 200 scientific papers,which have cumulatively been cited over 40,300 times with an h-index of 96. [2] [3] On the “Updated science-wide author databases of standardizes citation indicators”, [4] he is ranked 18th worldwide in the field of Biomedical Engineering. Zhang is also a co-founder and board member of Molecular Frontiers Foundation, [5] which organizes annual Molecular Frontiers Symposia in Sweden and around the world. [6] The selected winners are awarded Molecular Frontiers Inquiry Prize. [7]
Shuguang Zhang received his B.S. in biochemistry from Sichuan University in 1980 and Ph.D. in Biochemistry &Molecular Biology from University of California at Santa Barbara in 1988 (under mentorship of Eduardo Orias). The same year,he joined MIT to work with Alexander Rich.
In 1990,Shuguang Zhang made a serendipitous discovery of a self-assembling peptide in yeast protein Zuotin. [8] [9] This discovery led to the development of a new field of peptide nanobiotechnology and to designs of a variety of self-assembling peptides for widespread uses,including peptide hydrogels in materials science,3D tissue cell culture and tissue engineering,nanomedicine,sustained molecular releases,clinical and surgical applications. [10] [11] [12] [13] He co-founded a startup company 3DMatrix that brings the self-assembling peptide materials to human clinical for treatment of diabetic ulcers,bedsores (pressure ulcers) and for accelerated wound healings as well as surgical uses. [14] Many self-assembling peptide scaffold hydrogel products have received approvals from the US FDA,European Medicine Agency (EMA),Japan Medical Agency and medical approval agency in Chengdu,China. [15]
Less widely-known,Zhang invented the QTY Code as a systematic method of rendering insoluble peptide sequences water-soluble,to facilitate biochemical research,while retaining the native conformation and functionality. [16] [17] [18] [19] In 2011,Shuguang Zhang started to design membrane proteins,because there are ~26% of genes that code for membrane proteins in genomes which are crucial for both internal and external cellular communications. [20] [21] He conceived a simple molecular QTY Code,namely Glutamine (Q),Threonine (T) and Tyrosine (Y) to systematically replace the hydrophobic amino acids Leucine (L),Valine (V),Isoleucine (I),and Phenylalanine (F) in the 7 transmembrane alpha-helices of G protein-coupled receptors (GPCRs). [16] [18] Thus,it changes the water-insoluble form of membrane proteins,including GPCRs,into a water-soluble form. The QTY code results suggest that despite 46%-56% transmembrane alpha-helices changes,water-soluble QTY variants still maintain stable structures and biological function,namely,ligand-binding activities. This simple QTY code is a likely useful tool and has big impact for designs of water-soluble variants of previously water-insoluble and perhaps aggregated proteins,including amyloids. [16]
An alpha helix is a sequence of amino acids in a protein that are twisted into a coil.
Collagen is the main structural protein in the extracellular matrix of a body's various connective tissues. As the main component of connective tissue,it is the most abundant protein in mammals. 25% to 35% of a mammalian body's protein content is collagen. Amino acids are bound together to form a triple helix of elongated fibril known as a collagen helix. The collagen helix is mostly found in connective tissue such as cartilage,bones,tendons,ligaments,and skin. Vitamin C is vital for collagen synthesis,while Vitamin E improves its production.
G protein-coupled receptors (GPCRs),also known as seven-(pass)-transmembrane domain receptors,7TM receptors,heptahelical receptors,serpentine receptors,and G protein-linked receptors (GPLR),form a large group of evolutionarily related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. They are coupled with G proteins. They pass through the cell membrane seven times in the form of six loops of amino acid residues,which is why they are sometimes referred to as seven-transmembrane receptors. Ligands can bind either to the extracellular N-terminus and loops or to the binding site within transmembrane helices. They are all activated by agonists,although a spontaneous auto-activation of an empty receptor has also been observed.
Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the cell. Proteins can be targeted to the inner space of an organelle,different intracellular membranes,the plasma membrane,or to the exterior of the cell via secretion. Information contained in the protein itself directs this delivery process. Correct sorting is crucial for the cell;errors or dysfunction in sorting have been linked to multiple diseases.
Membrane proteins are common proteins that are part of,or interact with,biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane and can either penetrate the membrane (transmembrane) or associate with one or the other side of a membrane. Peripheral membrane proteins are transiently associated with the cell membrane.
A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently undergo significant conformational changes to move a substance through the membrane. They are usually highly hydrophobic and aggregate and precipitate in water. They require detergents or nonpolar solvents for extraction,although some of them (beta-barrels) can be also extracted using denaturing agents.
Peripheral membrane proteins,or extrinsic membrane proteins,are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins,or penetrate the peripheral regions of the lipid bilayer. The regulatory protein subunits of many ion channels and transmembrane receptors,for example,may be defined as peripheral membrane proteins. In contrast to integral membrane proteins,peripheral membrane proteins tend to collect in the water-soluble component,or fraction,of all the proteins extracted during a protein purification procedure. Proteins with GPI anchors are an exception to this rule and can have purification properties similar to those of integral membrane proteins.
A coiled coil is a structural motif in proteins in which 2–7 alpha-helices are coiled together like the strands of a rope. They have been found in roughly 5-10% of proteins and have a variety of functions. They are one of the most widespread motifs found in protein-protein interactions. To aid protein study,several tools have been developed to predict coiled-coils in protein structures. Many coiled coil-type proteins are involved in important biological functions,such as the regulation of gene expression —e.g.,transcription factors. Notable examples are the oncoproteins c-Fos and c-Jun,as well as the muscle protein tropomyosin.
Gramicidin,also called gramicidin D,is a mix of ionophoric antibiotics,gramicidin A,B and C,which make up about 80%,5%,and 15% of the mix,respectively. Each has 2 isoforms,so the mix has 6 different types of gramicidin molecules. They can be extracted from Brevibacillus brevis soil bacteria. Gramicidins are linear peptides with 15 amino acids. This is in contrast to unrelated gramicidin S,which is a cyclic peptide.
In chemistry,a cavitand is a container-shaped molecule. The cavity of the cavitand allows it to engage in host–guest chemistry with guest molecules of a complementary shape and size. The original definition proposed by Cram includes many classes of molecules:cyclodextrins,calixarenes,pillararenes and cucurbiturils. However,modern usage in the field of supramolecular chemistry specifically refers to cavitands formed on a resorcinarene scaffold by bridging adjacent phenolic units. The simplest bridging unit is methylene,although dimethylene,trimethylene,benzal,xylyl,pyridyl,2,3-disubstituted-quinoxaline,o-dinitrobenzyl,dialkylsilylene,and phosphonates are known. Cavitands that have an extended aromatic bridging unit,or an extended cavity containing 3 rows of aromatic rings are referred to as deep-cavity cavitands and have broad applications in host-guest chemistry. These types of cavitands were extensively investigated by Rebek,and Gibb,among others.
Bissulfosuccinimidyl suberate (BS3) is a crosslinker used in biological research. It is a water-soluble version of disuccinimidyl suberate.
HLA-G histocompatibility antigen,class I,G,also known as human leukocyte antigen G (HLA-G),is a protein that in humans is encoded by the HLA-G gene.
Andreas Mershin is a physicist at the Center for Bits and Atoms in the Massachusetts Institute of Technology.
A nanodisc is a synthetic model membrane system which assists in the study of membrane proteins. Nanodiscs are discoidal proteins in which a lipid bilayer is surrounded by molecules that are amphipathic molecules including proteins,peptides,and synthetic polymers. It is composed of a lipid bilayer of phospholipids with the hydrophobic edge screened by two amphipathic proteins. These proteins are called membrane scaffolding proteins (MSP) and align in double belt formation. Nanodiscs are structurally very similar to discoidal high-density lipoproteins (HDL) and the MSPs are modified versions of apolipoprotein A1 (apoA1),the main constituent in HDL. Nanodiscs are useful in the study of membrane proteins because they can solubilise and stabilise membrane proteins and represent a more native environment than liposomes,detergent micelles,bicelles and amphipols.
Self-assembling peptides are a category of peptides which undergo spontaneous assembling into ordered nanostructures. Originally described in 1993,these designer peptides have attracted interest in the field of nanotechnology for their potential for application in areas such as biomedical nanotechnology,tissue cell culturing,molecular electronics,and more.
Peptide amphiphiles (PAs) are peptide-based molecules that self-assemble into supramolecular nanostructures including;spherical micelles,twisted ribbons,and high-aspect-ratio nanofibers. A peptide amphiphile typically comprises a hydrophilic peptide sequence attached to a lipid tail,i.e. a hydrophobic alkyl chain with 10 to 16 carbons. Therefore,they can be considered a type of lipopeptide. A special type of PA,is constituted by alternating charged and neutral residues,in a repeated pattern,such as RADA16-I. The PAs were developed in the 1990s and the early 2000s and could be used in various medical areas including:nanocarriers,nanodrugs,and imaging agents. However,perhaps their main potential is in regenerative medicine to culture and deliver cells and growth factors.
In molecular biology,protein fold classes are broad categories of protein tertiary structure topology. They describe groups of proteins that share similar amino acid and secondary structure proportions. Each class contains multiple,independent protein superfamilies.
The peridinin-chlorophyll-protein complex is a soluble molecular complex consisting of the peridinin-chlorophyll a-protein bound to peridinin,chlorophyll,and lipids. The peridinin molecules absorb light in the blue-green wavelengths and transfer energy to the chlorophyll molecules with extremely high efficiency. PCP complexes are found in many photosynthetic dinoflagellates,in which they may be the primary light-harvesting complexes.
The SpyTag/SpyCatcher system is a technology for irreversible conjugation of recombinant proteins. The peptide SpyTag spontaneously reacts with the protein SpyCatcher to form an intermolecular isopeptide bond between the pair. DNA sequence encoding either SpyTag or SpyCatcher can be recombinantly introduced into the DNA sequence encoding a protein of interest,forming a fusion protein. These fusion proteins can be covalently linked when mixed in a reaction through the SpyTag/SpyCatcher system.
The QTY Code is a design method to transform membrane proteins that are intrinsically insoluble in water into variants with water solubility,while retaining their structure and function.