Collagen
Chronicles
Francis Crick has recorded his assessment of the gap in historiographical work on the discovery and characterization of the triple helix in his biography (1988) in this way:
“The basic fibre of collagen is made of three long chains wound around one another. Its discovery had all the elements that surrounded the discovery of the double helix. The characters were just as colourful and diverse. The facts were just as confused and the false solutions just as misleading. Competition and friendliness also played a part in the story. Yet nobody has written even one book about the race for the triple helix. This is surely because, in a very real sense, collagen is not as important a molecule as DNA.”
The chronicles in the space below mark a placeholder for the future work of historical scholarship that will be useful to the future members of the community of biophysics and structural biology researchers.
Introduction to the Collagen Problem
G N Ramachandran recounts the events leading to his work on collagen structure
In an interview in 1985, G N Ramachandran recalls encounters with two scientists because of whom he could begin his research on the molecular structure of collagen.
This rare video footage of Ramachandran is thanks to T Ramasami and CLRI. The full interview is available at the end of this page.
John Desmond Bernal, nicknamed ‘Sage’ by his friends and colleagues, was one of the founding figures in structural biology. He was born on 10 May 1901 in County Tipperary, Ireland. In 1919, he earned a scholarship to Emmanuel College, Cambridge for a Bachelor of Arts degree in mathematics and natural sciences, which he completed in 1923. Impressed by young Bernal’s potential, the mineralogist Arthur Hutchinson encouraged him to pursue x-ray crystallography and introduced him to William Henry Bragg. Bernal began his independent research career under W H Bragg at the Davy–Faraday Laboratory at the Royal Institution in 1923. He initially worked on inorganic materials like graphite and bronze. He developed an interest in organic matter, especially protein structures. This led him to focus on amino acids, sterols, and steroids. His most notable work during this stage would be describing the molecular structure of water and producing the first x-ray pattern of a globular protein in pepsin. His students included Dorothy Hodgkin, Max Perutz and Aaron Klug.
Bernal was deeply interested in the interplay between science and society. He believed the hallmark of any democracy was a healthy pursuit of scientific activities. By introducing the progress of the collagen structure problem to Ramachandran, Bernal was involved in the birth of structual biology in India. Ramachandran’s departments and Bernal’s academic lineage would be in close communication for decades after that fateful meeting in Chennai in 1952.
John Desmond Bernal (1901-1971)
A perspective on the shift to biomolecules and how someone like Nayudamma was important in Ramachandran’s beginnings in structural biology.
Yelavarthy Nayudamma, fondly remembered as ‘The People’s Scientist’, was a leading figure in Leather Research. He was born on 10 September 1922 into an agrarian community in the Guntur district of present day Andhra Pradesh. In 1942, Nayudamma completed a B.Sc in Chemical Technology at Banaras Hindu University. Towards the end of his degree, Nayudamma was inspired by the head of the Madras Institute of Leather Technology to pursue a course there. His interest in leather technology led him to an advanced training program in the University of Leeds, UK. He followed this with a doctorate in leather science under E R Theis at Lehigh University, USA. His doctoral research was exploring the tanning of leather using chromium salts. He returned to India in 1949 and was appointed the deputy director of the newly founded Central Leather Research Institute. He took charge as 2nd director of CLRI in 1958 when he was only 36. His tenure ended when he was appointed as the Director General of CSIR in 1971. He held many international posts as well, including the Senior Adviser Consultant to U.N. Agencies, UNDP Adviser, Global Research Committee UNDP. Governor, International Development Research Centre, Canada. President, COSTED.
Yelavarthy Nayudamma (1922-1985)
GNR’s history with CLRI and Y Nayudamma
T Ramasami, who regards both Ramachandran and Nayudamma as mentor figures in his career, shares his perception of their relationship. Their collaboration, which centered around collagen research, began in 1953 and continued till around 1970. How was the partnership between Ramachandran, a basic science researcher, and Nayudamma, an application-oriented scientist?
Collagen samples, why KTT, shark ray fin and Prof. P Sarma, head of the biochemistry department at Madras University.
Born and brought up in Alappuzha District in Kerala, Gopinath Kartha graduated with a B.Sc. (honours) degree in Physics and Mathematics from Presidency College, Madras in 1948; an MA degree in Physics from Madras University in 1949; and an M.Sc. degree from Andhra University, Vishakapatnam also in 1949. Later in 1949, he began his Ph.D in the Physics department of the IISc, Bangalore under G. N. Ramachandran. For his Ph.D. thesis, he solved the three-dimensional structure of Barium chlorate monohydrate. This was the first crystal structure solved by x-ray diffraction in India. He completed his Ph.D. in 1953 and followed this with a Post-Doctorate with Ramachandran, now in Madras University. This period would mark the beginning of his interest in biomolecules of medical importance and their structure determination, which was a major research focus throughout his career. Ramachandran and Kartha worked on the structure of the protein collagen. The Ramachandran-Kartha model of collagen was the first biomolecular structure, and the first fibrous protein structure, determined in India. After his post-doc, he spent brief periods at the Cavendish Laboratory in Cambridge (UK) and the National Research Council (NRC), Ottawa, Canada, before joining David Harker’s laboratory in 1959. The group was at the Brooklyn Polytechnic, New York when Kartha joined but soon after moved to the Roswell Park Memorial Institute, Buffalo, NY, where he would spend the rest of his career. In 1967, Harker and Kartha along with Jake Bello solved the structure of the enzyme ribonuclease. This was only the third globular protein structure ever determined, and the first one solved in the United States.
Gopinath Kartha was known to his friends to be research-minded, modest and a supportive colleague and mentor. He enjoyed doing his research but had a strong distaste for the publishing aspect of his work. Yet, the quality of his work and his research focus ensured his place in the history of Structural Chemistry and Biology.
Gopinath Kartha (1927-1984)
The Collagen structure before Ramachandran and Kartha
The 14 year history of collagen before GNR
What was known about collagen before Ramachandran begain working on it
What do the fibrous nature and amino acid composition of collagen mean for its protein structure? Manju Bansal answers this as she describes the information about collagen that Ramachandran and Kartha must have known as they began their investigations.
The Ramachandran and Kartha Model of Collagen
The collagen x-ray diffraction pattern developed by Gopalakrishna Ambady, one of the first students of the Department of Crystallography and Biophysics in Madras University.
How Ramachandran and Kartha developed their model of collagen
The pieces of the puzzle that was the structure of collagen was known to all the groups that were trying to solve it. How did Ramachandran and Kartha conceive of their model? What were the original ideas and breakthroughs in their model? Manju Bansal, P Balaram, K N Ganesh and N Srinivasan shed light on this matter.
The inspiration for the coiled-coil model
The key breakthrough in solving the structure of collagen was realizing that it is a coiled-coil. It is a testament to Ramachandran’s vivid imagination that he was inspired by similar geometric pattern in a completely unrelated phenomenon. T Ramasami recalls Ramachandran’s account of how he drew inspiration from a completely unrelated phenomenon in the universe.
Animation: Planetary motions and coiled coils
Animation by Rafeeque Mavoor
Why traditional crystallographers could not solve the collagen structure
UK was the birthplace of x-ray crystallography and structural biology and their scientists established the early methods in these fields. Yet, they could not solve structures like the alpha-helix and the collagen triple helix. Manju Bansal suggests a possible handicap they had in their techniques.
A twist in the tale of collagen
The shortcomings of the Ramachandran-Kartha model of collagen
Once Ramachandran and Kartha published their model of collagen, the global community of structural biologists were alerted of their research in Madras University. Their model was nicknamed the Madras Triple Helix by groups in Europe and America. However this model was not immediately accepted as a novel solution as Ramachandran had hoped. V Sasisekharan, N Srinivasan, George Rose, Manju Bansal, K N Ganesh describe the reasons for this.
How the collagen controversy affected GNR
An epilogue on the Ramachandran-Kartha model of collagen
Collagen and its significance
Perspective of scale of collagen in skin
The importance of collagen and the impact of knowing its structure
T Ramasami, a leather scientist; K N Ganesh, a biochemist, and Manju Bansal, a biophysicist, describe the importance of this protein found abundantly in the animal kingdom. They also discuss ongoing directions of basic and industrial research that have been enabled thanks to knowing the structure of collagen.
The structure-function relationship in collagen and collagen-like structures
KN Ganesh describes how the solution of the structure of collagen had an impact on protein structure research beyond the applications and uses of the collagen protein.
G N Ramachandran was interviewed by T Ramasami on the occasion of the inauguration of the Triple Helix Auditorium in CLRI in 1985. This rare video footage of Ramachandran is thanks to CLRI and T Ramasami. In this interview, Ramachandran describes how his department’s association with CLRI has impacted his work (and by extension, structural biology in India).