Histidine-rich peptides confer self-assembling properties to recombinant proteins through the supramole-cular coordination with divalent cations.This fact allows the cost-effective,large-scale generation of microscopic and macroscopic protein materials with intriguing biomedical properties.Among such materials,resulting from the simple bioproduction of protein building blocks,homomeric nano-particles are of special value as multivalent interactors and drug carriers.Interestingly,we have here identified that the assembly of a given His-tagged protein might render distin-guishable categories of self-assembling protein nanoparticles.This fact has been scrutinized through the nanobody-con-taining fusion proteins EM1-GFP-H6 and A3C8-GFP-H6,whose biosynthesis results in two distinguishable populations of building blocks.In one of them,the assembling and dis-assembling is controllable by cations.However,a second po-pulation immediately self-assembles upon purification through a non-regulatable pathway,rendering larger nano-particles with specific biological properties.The structural analyses of both model proteins and nanoparticles revealed important conformational variability in the building blocks.This fact renders different structural and functional categories of the final soft materials resulting from the participation of energetically unstable intermediates in the oligomerization process.These data illustrate the complexity of the His-mediated protein assembling in recombinant proteins but they also offer clues for a better design and refinement of protein-based nanomedicines,which,resulting from biologi-cal fabrication,show an architectonic flexibility unusual among biomaterials.

Eric Voltà-Durán;Julieta M Sánchez;Hèctor-López-Laguna;Eloi Parladé;Laura Sánchez-García;Alejandro Sánchez-Chardi;Ario de Marco;Ugutz Unzueta;Esther Vázquez;Antonio Villaverde

Institut de Biotecnologia i de Biomedicina,Universitat Autònoma de Barcelona,Bellaterra 08193,Barcelona,Spain;Departament de Genètica i de Microbiologia,Universitat Autònoma de Barcelona,Bellaterra 08193,Barcelona,Spain;CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN),Bellaterra 08193,Barcelona,Spain;Instituto de Investigaciones Biológicas y Tecnológicas(IIBYT)(CONICET-Universidad Nacional de Córdoba),ICTA&Cátedra de Química Biológica,Departamento de Química,FCEFyN,UNC.Av.Velez Sarsfield 1611,X 5016GCA Córdoba,Argentina;Basic Sciences Department,Faculty of Medicine and Health Sciences,Universitat Internacional de Catalunya,08195 Sant Cugat del Vallès,Spain;Servei de Microscòpia,Universitat Autònoma de Barcelona,Bellaterra 08193,Barcelona,Spain;Departament de Biologia Evolutiva,Ecologia i Ciències Ambientals,Facultat de Biologia,Universitat de Barcelona,08028 Barcelona,Spain;Laboratory for Environmental and Life Sciences,University of Nova Gorica,Nova Gorica 5000,Slovenia;Biomedical Research Institute Sant Pau(IIB Sant Pau),Sant Antoni Ma Claret 167,08025 Barcelona,Spain

中国科学：材料科学（英文）

[1]Eric Voltà-Durán;Julieta M Sánchez;Hèctor-López-Laguna;Eloi Parladé;Laura Sánchez-García;Alejandro Sánchez-Chardi;Ario de Marco;Ugutz Unzueta;Esther Vázquez;Antonio Villaverde-.The spectrum of building block conformers sustains the biophysical properties of clinically-oriented self-assembling protein nanoparticles)[J].中国科学：材料科学（英文）,2022(06):1662-1670

supramole,bioproduction,homomeric,guishable,A3C8,pulation,architectonic

spectrum,building,conformers,sustains,biophysical,properties,clinically,oriented,self,assembling,nanoparticles,Histidine,rich,peptides,confer,recombinant,proteins,through,cular,coordination,divalent,cations,This,fact,allows,cost,effective,scale,generation,microscopic,macroscopic,intriguing,biomedical,Among,such,resulting,from,simple,blocks,are,special,value,multivalent,interactors,drug,carriers,Interestingly,have,here,identified,that,assembly,given,tagged,might,categories,has,been,scrutinized,nanobody,taining,fusion,EM1,GFP,H6,whose,biosynthesis,results,two,distinguishable,populations,one,them,controllable,by,However,second,immediately,assembles,upon,purification,regulatable,pathway,rendering,larger,specific,biological,structural,analyses,both,model,revealed,important,conformational,variability,renders,different,functional,final,soft,participation,energetically,unstable,intermediates,oligomerization,process,These,data,illustrate,complexity,mediated,but,they,also,offer,clues,better,design,refinement,nanomedicines,which,fabrication,show,flexibility,unusual,among,biomaterials

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