Function via structure in vivo and in modeling

Detta är en avhandling från Johan Unge, c/o Olsson, västgötav 11, 22225 Lund

Sammanfattning: Knowledge of biomolecules three-dimensional structure has provided a detailed understanding of their function. In recent years the number of new protein sequences has far exceeded the number of protein experimental structure determinations. One goal of the new field of protein structural bioinformatics is to provide reliable and automated protein functional annotations and initial protein structure models based on sequence comparisons of target proteins of unknown structure to proteins of known structure. We present methods designed to address these goals, particularly for cases of sequence homology below what is needed by conventional sequence comparison methods. We found that combining structure and sequence information for families of evolutionarily-related proteins increases the sensitivity of sequence-to-structure comparison methods. The novelty of the method is in how the common structure elements in protein families are extracted and used in comparing sequences of target proteins with proteins where structure is known. The usefulness of the method was demonstrated in its ability to recognize distantly-related proteins with higher accuracy than when considering protein sequences only. The ribosome and its related factors are responsible for the synthesis of new proteins within cells. We have performed structural studies of two ribosomal proteins, L1 and L22, using X-ray crystallography. We verify a distinct movement between the two domains in L1 connected by a hinge region, from the comparison of the wild-type structure and a mutant structure. An open conformation of L1, with the two subunits considerably shifted from previous structures, was later verified to be active, confirming our results. The unusually elongated structure of L22 was determined for the first time and several clues were found that indicated extensive binding to ribosomal RNA. The structure and interaction with RNA was later confirmed in the structure of the complete large ribosomal subunit.

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