The PDB and the ribosome

This essay, which was written to commemorate the 50th anniversary of the Protein Data Bank, opens with some comments about the intentions of the scientists who pressed for its establishment and the nature of services it provides. It includes a brief account of the events that resulted in the determination of the crystal structure of the large ribosomal subunit from Haloarcula marismortui. The magnitude of the challenge the first ribosome crystal structures posed for the PDB is commented upon, and in the description of subsequent developments in the ribosome structure field that follows, it is pointed out that cryo-EM has replaced X-ray crystallography as the method of choice for investigating ribosome structure. This essay, which was written to commemorate the 50th anniversary of the Protein Data Bank, opens with some comments about the intentions of the scientists who pressed for its establishment and the nature of services it provides. It includes a brief account of the events that resulted in the determination of the crystal structure of the large ribosomal subunit from Haloarcula marismortui. The magnitude of the challenge the first ribosome crystal structures posed for the PDB is commented upon, and in the description of subsequent developments in the ribosome structure field that follows, it is pointed out that cryo-EM has replaced X-ray crystallography as the method of choice for investigating ribosome structure. The 50th anniversary of the Protein Data Bank (PDB) is an occasion worth celebrating. It has done everything its founders could possibly have hoped for. At the beginning, it was a tiny operation embedded in the Chemistry Department of Brookhaven National Laboratory. Today it is a large, multi-institutional organization (Rutgers, UCSD, and UCSF) that is part of international consortium called the Worldwide PDB, the members of which are the RSCB (USA), PDBe (Europe), PDBj (Japan), and the Biological Magnetic Resonance Data Bank (BMRB). The PDB would not exist today if a succession of public-spirited scientists had not devoted themselves to it. Walter Hamilton was its first manager, and following his untimely death in 1973, Tom Koetzle took over. Tom was succeeded by Joel Sussman in 1994. In 1999, the PDB was moved from Brookhaven to Rutgers, the home institution of its next director, Helen Berman. Fifteen years later, Helen was succeeded by Stephen Burley. We owe them a lot. Credit is also due to the managers of the agencies that have supported the PDB financially: primarily DOE, NSF, and NIH. At the time of it was founded, the PDB was a very strange duck indeed, and in the early 1970s, no one would have had any reason to be surprised if these agencies had refused to fund it. Happily, their managers understood the importance of the benefits that might be realized if some of the research funds they were responsible for were used to support an enterprise that was, and still is, a public utility. The rest, as they say, is history. As everyone knows, the PDB is a publicly accessible repository of information about the positions of atoms in biological macromolecules, and the essence of what it provides its users are sets of coordinates that specify the locations of most, if not all, of the atoms in particular macromolecules. Even though biochemists routinely use the word “structure” to describe these coordinate sets, it is important to realize that they are not structures. The structure of a macromolecule is the actual arrangement of its constituent atoms in three dimensions, about which our knowledge will always be imperfect to some degree. A coordinate set is an atomic model of a structure that rationalizes the by a particular done to it. The of the word “structure” with coordinate sets was of in the early of the PDB they were the by that had by X-ray It is to that have and it knowledge of a and the structures of its from crystal structures that have The is a of the coordinates and of a large of the atoms in the macromolecule of coordinates are of the positions of the atoms in the of a and the in their positions by crystal and model to them for the of to the which it is the of coordinates by the and if are to the of the and used to crystal they are This the the of the word “structure” to describe sets of atomic was In the the PDB has an of cryo-EM are by and if the of an is say, the of by these model will be the of in the of the out to its are some that will are still the of cryo-EM and the of it is to of from as to The of from which to in the PDB in the from their and In the first the of in the sets used to is the of atomic coordinates they and of them are not that the are with a of of which be that users for themselves they are by the it is the that a structure is by and the are of the structure. are the of in the PDB that are to the of are by atomic and them to the and This is an of an to as It is worth these in a public that with it would be to them in a from the PDB that users will not them with that supported The reason it is important to is a model that atomic positions as as and to a years who had information about from the structures in the PDB, that in are by they are by were that the from is about and they that the of the they are the that who are of the to is to about if were to about the in the in the X-ray of in the PDB, would that they all, the reason that these are This has not from the of which not and are not the as structures. with will be to as structures Even the structures in the PDB that have by what some might describe as crystallography and are not structures are as as and in be done about it the of structures are by the of the of the used to in is no of in the with which have and a it is these for a members about crystallography to a crystal and a set of coordinates to the one be surprised if the of a coordinate set might out to be it would have if the structure had by a in the the with which is a of in that It also to be pointed out that some of the structures in the PDB are they be the were in they not have the of and the of years to Helen that the PDB to the structures it them to the which in the of crystal structures would them the very was by in a of that of the structures in the PDB were not that they could to out that the PDB is an of and for that for model with the the PDB that is in is to the of coordinate sets, and it includes the of in the it to the public that users have As the information the PDB the them to their structures which is a The PDB might be to a that the in the coordinate in atomic are a that a crystal structure has It is to the of structures it is to the for X-ray crystal structures. The of the of by is very understood The of the of and it is a to the of the that some crystal would if its structure to the model for it. the of a model be by with The in for is for structures the the macromolecules. are by atomic and the of of biological in in to the and of the atoms in a an model also specify their which they It is not to information from is it would from if the still have some to the of their and the which it is is reason to be that these will be the of of of the PDB has to what was it and a about it to be of the had the time with a who was a of the that for its in what the field of was the time the PDB was no the that from the and of the The of that was and of the and an of scientists of them had would to the the were also from and as as from the users of It was that the which structures were was about to the of crystallography was and had the of it took to crystal structures. The PDB was set to with three of the by these public and As everyone knows, biochemists their in and for the of the out that the reason they are called is that the time the PDB was founded, they were actual of though that be to In that were by to called which were and were to the to the of the first crystal to be might a description of a a some in of an an the essence of the the had from their could be to the a In that crystal structures were not a the coordinates and of the atoms in some of which might be a that could be to the a of what that of for crystal structures. In the first were to the coordinates and of the atoms in a A of could a and what was to with a that the in these were as they still It is to of structures that are the information these it was for to themselves that the structures they had that the by the from their structures were the intentions of their structure to about a could the responsible to the were a of a might in the As for coordinates to were The was to with that a that might might not and by with of a tiny of what had was to the public a a structure. and in an to and his a that the crystal structure they had of in would have in a of It a of which were of the the and it was the first in a of in of which and were the and hoped that that a structure would a to the as as one and The of a the part of to the time to of the and were for. that the PDB has of no one would of a of that who has a any of the structures might in might in the of his not have to to the who about a crystal structure the from which it and its by for The PDB, of is the information to these and to the it is no to for the a structure has by the PDB, it has and the which agencies and public to structures as as they have It no who was the of the for an our and today is to that important years from and the the they be from the be This in its the responsible to the in the understood and realized that structure a of and public were to coordinate sets, were to and in his was used to that the repository of information about the structure of a crystal is the crystal to of some which the of the in which its structure was the from the of that for are to be as as the used to its structure to and with a of that structure the who first it. This to coordinate for who as Tom it is not a for It is for the if coordinates are the time structures are and if the from which coordinates were are also that structures be later, the who have the of the PDB provides a that its founders not have the of the determination of a the are to have sets and to have it to of sets and to the of they it be a for the members of their to the particular and set that to the of that and of the also be if the in the PDB, which is these the structure and the set will be to the members of the responsible for no what has for in the of the used to the that support the PDB and the which if they are not In the of the which a to be and also be the who still has a a for the information in the PDB still be in We be about the that have to use the in the PDB, three and is for a knowledge of the structures of the in some At the time the structure of a macromolecule is first it of what had about it by is not it is a that is are also the for the and of as the to structures the PDB provides is to biological scientists of the PDB of what is today about the structures of and and about the and structure. It is also a for in the structure and the structures in the PDB are of and of with and the PDB is for everyone research from structures. in that was one of the first to use the PDB In the in the atoms are in the of and the for the and of are still used The of and and the PDB has for who crystal structures. In the early of had to be At was done by also by the it had realized that the structures of also be a called which determination The of the The the that first of of structure be by that their structures are the as of of structure that have The the of structures in the PDB, of the the that the PDB will a and the are the in the of that are and their are were in the and by the a their of was understood by it was that are of the the large ribosomal subunit about the of the the ribosomal subunit and that the the and that that the is the includes the that the of about the of the the if was that important the of would if atomic crystal structures could be of were that in by it was not that the first of were that were large to with of the large ribosomal from It a time to the structures of were first in the early of the the of X-ray crystallography it was not that the first atomic crystal structure of was of A The atomic the time that the first of ribosome and the first atomic ribosome structures was next to to of the large ribosomal from The atomic structure of the large ribosomal subunit A of ribosomal subunit A of the ribosomal by crystallography was a and in it is to it took their are large, and their due to in the first were also not that the of the from them were in later, of and ribosomal from not were ribosome and for of of large ribosomal from Haloarcula to A by the early the was It had that sets be from ribosome X-ray and the X-ray by of ribosomal At that the that was a to ribosome and it was not to about it. the one was out of the were no structures in the PDB that were to of ribosomal the the for also atoms to in in that not their structures and the in the of the in the of is large, as it is for ribosome a large of atoms will have to be to to The is that the the of the the the of it is to for any The is that if the of is large, it be to their locations from the in they and if that be no information will be the had the to by the the of the of three of them are to of and The was by of the of the to atomic the might have had a time what to in a that the of and his the structure of the from and it includes a of information about what his The to the of the not they it. has written Tom in the of the the with the crystal structure of the from Haloarcula Tom and had about ribosome crystallography the It had the ribosome for of and had its organization for years by in A of the in the ribosomal subunit of a to the of the information had by was to it was to if could be Tom was the ribosome is the of the in and in was to the crystal structures of as of them as of the was to the of the ribosome in of these that if Tom was to a to the would the very support might Tom to that and moved to in the of was not for the of the one was no that would in ribosome was an the if it could be it was that might it In moved to a was in and as had of its that the was no to it had was in no of Even the of the model of the ribosome that and his had from cryo-EM that the to structure determination had a to that ribosome could be by of of the was to important were as to that the time it would have to a of ribosome crystal of our would the that had to the which were the of the from that had first a and for of of large ribosomal from Haloarcula to A would cryo-EM ribosome as the that the had with the and some that and his could the cryo-EM model We that the of the model hoped would was to and the of the it was used for would be no also realized that a set of that in would have a our to information from would to use to the atoms had in our The of the the is to the of atoms is the of in the will also be and the of in the will be that of a the of in the which is from that the of are will be and their positions will be by the and of of the to in the by the positions of is a say, it to information from to also out to the to if they would of the they had The reason were is a that atoms of atomic will about the a would that in the of be if a of these and if the is it will be to their locations The with is that the of the a to very as and in the of it is no would be if atoms of the of had to the the to the was to This to had for our to our it was not to be to out to the of the were sets would As it sets of could be from the the National that were by and his for the of in had to not some of the had with that them also were not was it to the time would time in the We could of these it to from to Brookhaven National was is was years As would have it is always to have of the first which with to a in the of the of the was the of which could by about the time was these were that had the and that had the and to of the the from the of were not the which was At about and his and the model they had for the A of their model in the of the was that was also with of the from The for the X-ray and the of a in the of the the of which was to the one that had for it At that the ribosome had it was also to the are in the of which out to be that were The the of the by these was about the as that of the by the which would not have The the crystal out to be a in a had from in which the was could be used to our for the from that the the of in the used to the of in these was would be if the was by as as would with no of Tom a to the in and by early and had a of the from that had by and three the used to and the from it were in a in A A X-ray of the large ribosomal it is the important of the of the it that structures be from ribosome had sets were no and the to sets that to of the by our also the National which was A later, a of the from these sets of and structures a A of the ribosomal of the used to that was by It to in the and that would have if had not The was it was from that that the of and was to the with any could was that to ribosomal of structure and structures the to the of atomic has in cryo-EM of the of these a called the that is in structure was and a that for in that have a structure was used to that particular in the our it of one the subunit of the about the to be the of a of and the a that no the structure was that of a that was a three of and that the structure in the of that is to that of the in the of the of the The had the The of the which as they are was in the and that of and out of its the positions had to the were of was a and of the it to the are the In the of 1999, a our was the to the ribosome was in were by of the in ribosome Tom for the The crystal structure of the large ribosomal subunit A The and for and the of his was to that of the of and structures a A of the ribosomal the his had with the from for which had a the crystal structure of a ribosomal The and as a to of the it was the first time had in public about his that and had the possibly of the that had and that they had to the for which they had a of ribosomal in of ribosomal The and with the of some his had and with the they were with of the ribosome from for which they had a the structure and of by use of and X-ray The and for by the of the it was to that atomic structures for and ribosomal were The of the ribosome to was of its members had to the structure of the ribosome a of and they were by the that the they had and to would In the the of the what could to them for the ribosome The and for pointed out that structures they would be to use their to the ribosome they had to out which out to be not they were that a the the first of the that had a that could be it and by the magnitude of the that It was The were for that was to the part of the that to was the of the by the large of it took to the it was in some were to for one of which to a that of any had the a structure of the from that and a structure of the subunit with a of the The atomic structure of the large ribosomal subunit A The of ribosome in later, and a structure of the that they had from a of ribosomal subunit A and a of the structure that was a of the ribosomal We no a of the that from these structures. In the first they that the for the structures of the three that had by were first had years structure of ribosomal structure model for ribosomal the structure of the with a that the that is of The of ribosome in It also that in a in the with which are from the structure of the ribosomal subunit and its with could no be any the ribosome is a the of ribosomal out to be had of a that has a from the of which is by its with and a are some The of ribosomal that have which to be the of and the their of the the of the the of the that is in the of that is about the as it is its and important of all, these structures the about and the which is what atomic structures of have for biochemists the first one was in of A it was that the of the of the PDB had to the of what an of ribosome structures. were for the PDB are The of the ribosome is and it of three and to of have no which that the of the of a ribosome crystal is an of the of an a ribosomal the of structure in a ribosome be to that of to and the sets are It is a to the PDB that it it had to not that structures be in the PDB to also that they be to the public that was We had a and our structure a of time and structure be a to the of our the one who has the managers and were no no In the they were in as a were to with our structure for that by the time they would have them to it. the crystal structure of a macromolecule is it is to the structures of of the it with to the that the three ribosome structures were by of structures that these and ribosomal with the of of the PDB, of these was as as the first had was to be no for the The ribosome which from and were by ribosome structures from structure of the large ribosomal subunit from a and X-ray crystal structures of the and a ribosome from were by the ribosome structures as the one was in the surprised that had to these structures. had that the structures of are of ribosomal an supported by of ribosomal It be in that if a structure be by the of time it will to to will be it would have if it had the model will the of the these ribosome structures also as for of from are as large as and the of these of are are and for ribosomal it was not that the for the of of by structures would be to be they to the determination of the crystal structure of the ribosome structure of the and the ribosomal subunit from structure of the ribosomal subunit in with the of the first crystal the of ribosome crystallography to a the has as the method of choice for the structures of large the with its are its to with the tiny of it and of the that is not structure determination by cryo-EM is not as as it is to be of the of to in with for ribosome for cryo-EM were the took A model for of the and cryo-EM has a large of ribosome structures might still be for if crystallography was the our them are structures for of the in the that are to of ribosome and by the for ribosome of the large ribosomal and for of the large ribosomal The structure of the large subunit of the and of the A that the that had in by the of the first ribosome crystal structures would structures had for a in the about the and it might have done for the of the of ribosomal and their is an important in and in it is in its is an still to be about and cryo-EM is the for investigating its an cryo-EM has not that are from the of and which from also that they in structure from one to the next and of the it is by these cryo-EM is to an important part in these the of a of that its of in the to and as it to the PDB is to an important in it The that they have no of with the of for out the of the events that as the structure of the was and for the of that in is responsible for of of and of devoted his to the of and to the and of the the Protein Data Bank to the part of Biological of the 50th anniversary of the Protein Data Bank the of biological structures. The of the PDB is have a of in to its an of is a of the the PDB and the in of information has had and some of the as